Publications by authors named "David Meyre"

173 Publications

Effects of supplementation on blood concentration and mRNA expression of TNF-, PPAR- and adiponectin, as major adipogenesis-related markers, in obese and overweight women: a crossover, randomised-controlled trial.

Br J Nutr 2022 May 11:1-10. Epub 2022 May 11.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Adipocyte expansion through adipogenesis can offset the adverse metabolic effects of obesity. (NS) (black seed) oil is shown to have therapeutic features in the management of obesity. NS oil might have beneficial changes in obese populations through mediating serum levels of adipogenesis-related parameters and relative transcriptional gene-diet interactions (nutrigenomics), though no previous studies assessed this mechanism in overweight/obese participants. This study assessed the effects of NS oil supplements on blood concentration and mRNA expression levels of TNF-, PPAR- and serum adiponectin and expression of , as major adipogenesis and obesity-related parameters, in overweight/obese women using a cross-over design. Eligible women were randomised to receive either NS oil supplements (2000 mg/d) or placebo. Two periods of interventions (8 weeks in each) were cross-changed by a 4-week washout period. An individualised diet plan without calorie deficits was given to participants to match their energy/macronutrient intakes. The Pkcross procedure and intention-to-treat analysis were performed using Stata. was estimated to measure the magnitude of the effects. Forty-six participants were included. NS oil capsules reduced transcription levels (( = -2·31), < 0·001) and blood concentrations of TNF- (( = -0·29), < 0·001). AdipoR1 expression ( = 2·24, < 0·001) and serum adiponectin ( = 0·88, < 0·001) showed a significant augmentation with a medium-high effect size, as did gene expression ( = 0·69, < 0·001) and serum levels of PPAR- ( = 0·97, < 0·001). There was a moderate but significant decrease in body weight ( = 0·6, < 0·001). The present beneficial findings would provide strong information for future nutrigenomics/clinical trial studies assessing the role of NS in the management of obesity and other comorbidities.
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http://dx.doi.org/10.1017/S0007114522001428DOI Listing
May 2022

Low-frequency Coding Variants Associated With Body Mass Index Affect the Success of Bariatric Surgery.

J Clin Endocrinol Metab 2022 02;107(3):e1074-e1084

Inserm UMR_S1256 Nutrition-Genetics-Environmental Risk Exposure, University of Lorraine, 54500 Nancy, France.

Context: A recent study identified 14 low-frequency coding variants associated with body mass index (BMI) in 718 734 individuals predominantly of European ancestry.

Objective: We investigated the association of 2 genetic scores (GS) with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery.

Methods: The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective GS based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study.

Results: While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they affect BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery.

Conclusion: Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also affect the outcomes of bariatric surgery in patients with severe/morbid obesity.
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http://dx.doi.org/10.1210/clinem/dgab774DOI Listing
February 2022

The effect of vitamin D supplementation on serum levels of fibroblast growth factor- 23: A systematic review and meta-analysis of randomized controlled trials.

J Steroid Biochem Mol Biol 2022 01 25;215:106012. Epub 2021 Oct 25.

Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran. Electronic address:

Previous studies of the effect of vtamin D on serum levels of fibroblast growth factor- 23 (FGF-23) have yeilded an inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to investigate the effect of vitamin D supplementation on serum levels of FGF-23. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to November 2020, for RCTs that evaluated the effects of native or active vitamin D supplementation on serum levels of FGF-23 in adults. Weighted mean difference (WMD) were calculated and random effects meta-analysis was used to estimate the overall effects. Twenty-seven trials were included in the meta-analysis. Supplementation with native vitamin D (23 studies, n = 2247 participants; weighted mean difference [WMD] = 0.5 pg/mL, 95 % CI: -0.52 to 1.51, P = 0.33; I = 29.9 %), and active vitamin D (5 studies, n = 342 participants, WMD = 29.45 pg/mL, 95 % CI: -3.9 to 62.81, P = 0.08; I = 99.3%) had no significant effects on serum FGF-23 concentration. In subgroup analyses, supplementation with ergocalciferol (3 studies, n = 205 participants; WMD = 18.27 pg/mL, 95 % CI: 5.36-31.17, P = 0.006), and daily dosing regimens (9 studies, n = 1374 participants; WMD = 0.41 pg/mL, 95 % CI: 0.22 to 0.59, P < 0.001) increased serum FGF-23 levels compared to control. Overall, our findings revealed no significan effect of vitamin D supplementation on serum FGF-23 concentration. However, further high quality, large-scale studies are needed to better elucidate this relationship.
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http://dx.doi.org/10.1016/j.jsbmb.2021.106012DOI Listing
January 2022

Consequences of Paternal Nutrition on Offspring Health and Disease.

Nutrients 2021 Aug 17;13(8). Epub 2021 Aug 17.

Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (Inserm), Université de Lorraine, F-54000 Nancy, France.

It is well established that the maternal diet during the periconceptional period affects the progeny's health. A growing body of evidence suggests that the paternal diet also influences disease onset in offspring. For many years, sperm was considered only to contribute half of the progeny's genome. It now appears that it also plays a crucial role in health and disease in offspring's adult life. The nutritional status and environmental exposure of fathers during their childhood and/or the periconceptional period have significant transgenerational consequences. This review aims to describe the effects of various human and rodent paternal feeding patterns on progeny's metabolism and health, including fasting or intermittent fasting, low-protein and folic acid deficient food, and overnutrition in high-fat and high-sugar diets. The impact on pregnancy outcome, metabolic pathways, and chronic disease onset will be described. The biological and epigenetic mechanisms underlying the transmission from fathers to their progeny will be discussed. All these data provide evidence of the impact of paternal nutrition on progeny health which could lead to preventive diet recommendations for future fathers.
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http://dx.doi.org/10.3390/nu13082818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400857PMC
August 2021

Genetic syndromes with diabetes: A systematic review.

Obes Rev 2021 09 15;22(9):e13303. Epub 2021 Jul 15.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Previous reviews and clinical guidelines have identified 10-20 genetic syndromes associated with diabetes, but no systematic review has been conducted to date. We provide the first comprehensive catalog for syndromes with diabetes mellitus. We conducted a systematic review of MEDLINE, Embase, CENTRAL, PubMed, OMIM, and Orphanet databases for case reports, case series, and observational studies published between 1946 and January 15, 2020, that described diabetes mellitus in adults and children with monogenic or chromosomal syndromes. Our literature search identified 7,122 studies, of which 160 fulfilled inclusion criteria. Our analysis of these studies found 69 distinct diabetes syndromes. Thirty (43.5%) syndromes included diabetes mellitus as a cardinal clinical feature, and 56 (81.2%) were fully genetically elucidated. Sixty-three syndromes (91.3%) were described more than once in independent case reports, of which 59 (93.7%) demonstrated clinical heterogeneity. Syndromes associated with diabetes mellitus are more numerous and diverse than previously anticipated. While knowledge of the syndromes is limited by their low prevalence, future reviews will be needed as more cases are identified. The genetic etiologies of these syndromes are well elucidated and provide potential avenues for future gene identification efforts, aid in diagnosis and management, gene therapy research, and developing personalized medicine treatments.
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http://dx.doi.org/10.1111/obr.13303DOI Listing
September 2021

Effect of sex/gender on obesity traits in Canadian first year university students: The GENEiUS study.

PLoS One 2021 16;16(2):e0247113. Epub 2021 Feb 16.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.

Background: While weight gain during first year of university has been well documented in North America, literature on sex-specific effects is scarce and inconsistent. The objective of this investigation was to explore sex-specific changes in obesity traits during first year of university at McMaster University (Ontario, Canada).

Methods: 245 first-year students (80.4% females) were followed longitudinally with data collected early in the academic year and towards the end of the year. Obesity parameters including weight, waist and hip circumferences, BMI, and waist to hip ratio were investigated. The Mann-Whitney U test and the Wilcoxon signed-rank test were used for pairwise comparison of traits in the absence of adjustments. Additionally, the repeated-measures ANOVA test was used with covariate adjustments to investigate the interaction between sex and time.

Results: Overall sample trends indicated a significant increase in mean weight by 1.55 kg (95% CI: 1.24-1.86) over the school year (p<0.001). This was accompanied by significant gains in BMI, and waist and hip circumferences (p<0.001) in the overall sample. At baseline, males presented with higher body weight, BMI, waist and hip circumferences, and WHR, as compared to their females counterparts (p<0.01). Additionally, sex-stratified analysis indicated significant gains in weight, BMI, and waist and hip circumferences in both males and females (p<0.01). However, a comparison of the magnitude of change over time between the two sex groups revealed no significant difference for any of the investigated traits (p>0.05).

Conclusion: While our study confirms significant weight gain in both male and female first year university students in Ontario, Canada, it does not show sex specific differences within this context. Our investigation highlights the importance of accounting for sex and gender in health research and supports the need of further studies in this area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247113PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886219PMC
September 2021

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.

Sci Rep 2021 02 4;11(1):3097. Epub 2021 Feb 4.

Department of Health Research Methods, Evidence, and Impact, Michael DeGroote Centre for Learning and Discovery, McMaster University, Room 3205, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35-2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13-2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14-3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.
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http://dx.doi.org/10.1038/s41598-021-82728-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862248PMC
February 2021

AGT rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy.

J Diabetes Complications 2021 03 31;35(3):107826. Epub 2020 Dec 31.

Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico. Electronic address:

Aims: Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D).

Methods: We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates.

Results: AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, β = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, β = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, β = 2.837 ± 1.267, p = 0.026).

Conclusion: Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107826DOI Listing
March 2021

The effect of race/ethnicity on obesity traits in first year university students from Canada: The GENEiUS study.

PLoS One 2020 25;15(11):e0242714. Epub 2020 Nov 25.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Background: Little is known about the impact of race/ethnicity on weight change at university. The objective of this study is to determine if ethnicity has an impact on obesity traits in a multiethnic cohort of first-year students at McMaster University in Ontario, Canada.

Methods: 183 first year students from the three most represented ethnic groups (South Asian, East Asian, and white-Caucasian) in our study sample were followed longitudinally with data collected early in the academic year and towards the end of the year. Obesity parameters including body weight, body mass index (BMI), waist and hip circumference, and waist hip ratio (WHR) were analyzed. The Wilcoxon signed-rank test was used for pairwise comparison of traits from the beginning to the end of the year in the absence of adjustments. Linear regression was used with covariate adjustments to investigate the effect of ethnicity on obesity traits.

Results: A significant increase in weight by 1.49 kg (95%CI: 1.13-1.85) was observed over the academic year in the overall analyzed sample. This was accompanied by significant gains in BMI, waist and hip circumferences, and WHR. Ethnicity stratified analysis indicated significant increase in all investigated obesity traits in East Asians and all traits, but WHR, in South Asians. White-Caucasians only displayed significant increases in weight and BMI. Body weight and hip circumference were significantly lower in East Asians compared to white-Caucasians at baseline. However, East Asians displayed a significantly larger increase in mean BMI and weight compared to white-Caucasians after first-year. South Asians displayed larger waist circumference at baseline compared to East Asians and larger WHR compared to white-Caucasians.

Conclusion: Our findings demonstrate that ethnicity has an impact on obesity traits in first-year university students. Universities should take ethnicity into account while implementing effective obesity prevention programs to promote healthy and active lifestyles for students.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242714PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688123PMC
January 2021

Association of gut microbiome with fasting triglycerides, fasting insulin and obesity status in Mexican children.

Pediatr Obes 2021 05 15;16(5):e12748. Epub 2020 Nov 15.

Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.

Background: The association of gut microbiota with obesity and its cardio-metabolic complications in paediatric populations is still controversial.

Objective: We investigated the association of obesity and cardio-metabolic traits with gut microbiota on 167 and 163 children with normal weight and obesity from Mexico City and Oaxaca, Mexico.

Methods: Anthropometric and biochemical traits were measured. The microbial communities were determined by high-throughput sequencing of bacterial 16S rRNA gene v3-v4 region.

Results: The gut microbial community structure was associated with obesity and fasting plasma insulin (FPI) in Mexico City (P = 0.012, P = 0.0003) and Oaxaca (P = 0.034, P = 0.016), and with triglycerides (TG) in Oaxaca (P = .0002). The Firmicutes/Bacteroidetes ratio was positively associated with TG in Oaxaca (P = .003). Firmicutes and Bacteroidetes phyla were positively and negatively associated with obesity (Mexico City: P = 0.013, P = 0.009) and TG (Oaxaca: P = 0.002, P = 0.004). In Oaxaca, Verrucomicrobia was negatively associated with obesity (P = .004). In Mexico City, the bacterial genus Fusicatenibacter, Romboutsia, Ruminococcaceae, Ruminiclostridium, Blautia, Clostridium, Anaerostipes and Intestinibacter were associated with obesity and FPI, while in Oaxaca, Bacteroides, Alistipes and Clostridium were associated with TG.

Conclusion: The gut microbial community structure in children is associated with obesity and FPI in Mexico City, and with obesity, FPI and TG in Oaxaca.
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http://dx.doi.org/10.1111/ijpo.12748DOI Listing
May 2021

Effect of living arrangement on anthropometric traits in first-year university students from Canada: The GENEiUS study.

PLoS One 2020 6;15(11):e0241744. Epub 2020 Nov 6.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Background: The transition to university often involves a change in living arrangement for many first-year students. While weight gain during first year of university has been well documented, Canadian literature on the impact of living arrangement within this context is limited. The objective of this investigation was to explore the effect of living arrangement on anthropometric traits in first-year university students from Ontario, Canada.

Methods: 244 first-year undergraduate students were followed longitudinally with data collected early in the academic year and towards the end of the year. Anthropometric parameters including weight, waist and hip circumference, body mass index (BMI), and waist-to-hip ratio (WHR) were examined. The Wilcoxon signed-rank test was used for pairwise comparison of traits from the beginning to end the year in the absence of adjustments. Additionally, linear regression models with covariate adjustments were used to investigate effect of the type of living arrangement (i.e. on-campus, off-campus, or family home) on the aforementioned traits.

Results: In the overall sample, a significant weight increase of 1.55kg (95% CI: 1.24-1.86) was observed over the school year (p<0.001), which was also accompanied by significant gains in BMI, and waist and hip circumferences (p<0.001). At baseline, no significant differences were found between people living on-campus, off-campus, and at home with family. Stratified analysis of change by type of living arrangement indicated significant gains across all traits among students living on-campus (p<0.05), and significant gains in weight and BMI among students living at home with family. Additionally, a comparison between living arrangements revealed that students living on campus experienced significantly larger gains in weight and BMI compared to students living off-campus (p<0.05).

Conclusion: Our findings indicate that living arrangement is associated with different weight gain trajectories in first-year university students.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241744PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647062PMC
January 2021

Signatures of natural selection and ethnic-specific prevalence of NPC1 pathogenic mutations contributing to obesity and Niemann-Pick disease type C1.

Sci Rep 2020 11 2;10(1):18787. Epub 2020 Nov 2.

Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Michael G. DeGroote Centre for Learning and Discovery Room 3205, Hamilton, ON, L8S 4K1, Canada.

While homozygous pathogenic mutations in the NPC1 gene cause Niemann-Pick type C1 disease, heterozygous mutations cause highly-penetrant obesity. We aimed to investigate the prevalence of NPC1 mutations and their signatures of natural selection in 122,678 exome sequenced participants from six ethnic groups in the Genome Aggregation Database. Pathogenic missense coding mutations were identified by in silico tools and the ClinVar database. Signatures of natural selection were assessed by the probability of NPC1 being loss-of-function mutation intolerant and Z-scores of observed/expected synonymous and non-synonymous mutation ratios. There was no evidence of negative selection observed for synonymous, non-synonymous and loss-of-function mutations. However, there were significant ethnic differences in the prevalence of heterozygous pathogenic NPC1 mutations ranging from 0.56% in Ashkenazi Jewish to 3.26% in African/African Americans (5.8-fold difference). Four homozygous carriers of pathogenic NPC1 mutations were also identified, belonging to the South Asian population. In conclusion, NPC1 mutations are consistent with a model of balanced selection, where heterozygotes and homozygotes have higher and lower reproductive fitness, respectively. Therefore, NPC1 heterozygous mutations may account for a substantial and ethnic-dependent percentage of obesity in the general population, while NPC1 homozygous mutations may be frequent in the South Asian populations and warrants more investigation.
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http://dx.doi.org/10.1038/s41598-020-75919-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608643PMC
November 2020

Sex/Gender Modifies the Association Between the MC4R p.Ile269Asn Mutation and Type 2 Diabetes in the Mexican Population.

J Clin Endocrinol Metab 2021 01;106(1):e112-e117

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Context: Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency affects body weight in a sex-/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce.

Objective And Design: We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6929 Mexican adults (3175 T2D cases and 3754 normal glucose tolerance [NGT] controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using TaqMan technology.

Results: The MC4R p.Ile269Asn mutation was associated with T2D in 6929 Mexican adults (Ncontrols = 3754, Ncases = 3175, odds ratio [OR] = 2.00, 95% confidence interval [CI], 1.35-2.97; P = 5.7 × 10-4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (P = 0.049). Although a strong association between the mutation and T2D was observed in men (Ncontrols = 2418, Ncases = 1807, OR = 2.63, 95% CI, 1.62-4.28, P = 9.3 × 10-5), results were not significant in women (Ncontrols = 1336, Ncases = 1368, OR = 1.16, 95% CI, 0.60-2.26, P = 0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex-/gender-specific pattern of association (men: OR = 2.22, 95% CI, 1.34-3.67, P = 0.0019; women: OR = 1.02, 95% CI, 0.51-2.02, P = 0.95).

Conclusion: This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.
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http://dx.doi.org/10.1210/clinem/dgaa726DOI Listing
January 2021

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

PLoS Genet 2020 10 12;16(10):e1008718. Epub 2020 Oct 12.

Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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http://dx.doi.org/10.1371/journal.pgen.1008718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581004PMC
October 2020

Circulating levels of CTRP3 in patients with type 2 diabetes mellitus compared to controls: A systematic review and meta-analysis.

Diabetes Res Clin Pract 2020 Nov 17;169:108453. Epub 2020 Sep 17.

Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Growing evidence suggests that adipokines may be therapeutic targets for cardiometabolic diseases such as type 2 diabetes mellitus (T2DM). C1q TNF Related Protein 3 (CTRP3) is a newly discovered adipokine which shares properties with adiponectin. The literature about the association between circulating levels of CTRP3 and T2DM has been conflicting. The present study reassessed the data on circulating CTRP3 levels in T2DM patients compared to controls through a systematic review and meta-analysis. A literature search was performed in Medline, Embase, Scopus, and Web of science to identify studies that measured circulating CTRP3 levels in T2DM patients and controls. The search identified 124 studies of which 59 were screened for title and abstract and 13 were subsequently screened at the full text stage and 12 studies included into the meta-analysis. Subgroup analyses, depending on the presence of T2DM complications, matching for BMI, age, and cut off value of fasting blood sugar and HOMA-IR, were performed. The results show that circulating CTRP3 levels are negatively associated with T2DM status (SMD: -0.837; 95% CI: (-1.656 to -0.017); p = 0.045). No publication bias was identified using the Begg's rank correlation and Egger's linear regression tests (P = 1 and P = 0.44, respectively). Meta-regression demonstrated significant association between CRTP3 levels with BMI (slope: 0.11; 95% CI: 0.04-0.19; p = 0.001) and sex (slope: -0.07; 95% CI: -0.12 to -0.01; p = 0.008). The present systematic review and meta-analysis evidences a negative association between circulating level of CTRP3 and T2DM status. BMI and sex may modify this association.
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http://dx.doi.org/10.1016/j.diabres.2020.108453DOI Listing
November 2020

Identifying factors associated with obesity traits in undergraduate students: a scoping review.

Int J Public Health 2020 Sep 5;65(7):1193-1204. Epub 2020 Sep 5.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Objectives: This scoping review identifies factors associated with obesity traits including body mass index, weight, and body fat percentage in undergraduate students.

Methods: We searched CINAHL, EMBASE, MEDLINE, and PsycINFO for original studies of undergraduate students where an obesity trait was associated with a risk factor.

Results: Two-hundred sixty-eight articles were included comprising of 251 studies: 186 cross-sectional, 50 cohort, 11 interventional, and 4 qualitative. We extracted data on risk/protective factors, obesity traits, and the direction of effect between them. We identified a variety of factors including age, sex, ethnicity, socioeconomic status, religion, diet, eating habits, physical activity, sedentary activity, sleep, stress, university campus life, alcohol use, smoking, psychiatric disorders, body image, eating attitude, eating regulation, personality, sociocultural influences, and genetics. The majority of associations were cross-sectional. For longitudinal findings, usually only one study investigated each trait.

Conclusions: This review identifies a need for higher quality evidence to support results from cross-sectional studies and replication of findings of longitudinal studies. This review identifies gaps in the literature, generates hypotheses, guides researchers to plan future studies, and helps decision-makers design obesity-prevention programs in universities.
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http://dx.doi.org/10.1007/s00038-020-01458-4DOI Listing
September 2020

Medium term post-bariatric surgery deficit of vitamin B12 is predicted by deficit at time of surgery.

Clin Nutr 2021 01 25;40(1):87-93. Epub 2020 Apr 25.

Inserm UMRS 1256 N-GERE (Nutrition-Genetics-Environmental Risks) - University de Lorraine, Faculty of Medicine, Nancy, France; Department of Endocrinology Diabetology and Nutrition, Regional University Hospital of Nancy (CHRU Nancy), Nancy, France. Electronic address:

Background: Patients with morbid obesity have a high risk of deficits in micronutrients, after bariatric surgery. The reasons why systematic use of multivitamin and trace element supplements cannot prevent all deficits are complex and should deserve more attention. Little is known about the influence of micronutrient deficits at surgery.

Aim: This present study aimed to explore the deficit in vitamin B12 vs other micronutrients during the follow-up of a French cohort of cases with bariatric surgery under systematic multivitamin/trace elements supplementation and to determine whether it was influenced by clinical, metabolic characteristics at surgery.

Methods: We prospectively enrolled obese patients with bariatric surgery (laparoscopic gastric bypass or laparoscopic sleeve gastrectomy) between 2013 and 2018 (OBESEPI/ALDEPI Cohort, NCT02663388). They received a daily multivitamin/micronutrients supplement. Follow-up data at 4 visits, 2, 12, 18 and 24 months after surgery, were collected.

Results: The highest rate of deficits was observed at visit 1 for vitamin D (35.7%), iron (21.9%) and folate (10.2%). Except B12, the deficits of all micronutrients decreased in later visits. In contrast, cases with vitamin B12 deficit decreased from 13.5% at surgery to 2.0% at visit 1, and increased in later visits, with a maximum of 12.0% at visit 3. Vitamin B12 concentration at surgery was the single predictor of B12 deficit at visit 3. It was also associated with age, and APRI score, an index of nonalcoholic fatty liver disease (NAFLD), in multivariate analysis.

Conclusions: The failure of systematic supplementation with multivitamin/trace elements tablets to prevent specific deficits illustrates the need for adapted specific supplementations, in some cases. The worsening of B12 deficit rate in the 18-24 months follow-up depends in part to low B12 at time of surgery. A special consideration should be devoted to this subset of patients. The cohort study was registered at clinicaltrials.gov as NCT02663388.
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http://dx.doi.org/10.1016/j.clnu.2020.04.029DOI Listing
January 2021

Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children.

Pediatr Obes 2020 08 20;15(8):e12641. Epub 2020 Apr 20.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Background: Mexican children are characterized by a high-starch intake diet and high prevalence of obesity.

Objectives: To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls.

Methods: Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed.

Results: A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (P = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children.

Conclusions: Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.
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http://dx.doi.org/10.1111/ijpo.12641DOI Listing
August 2020

Causal Association of Haptoglobin With Obesity in Mexican Children: A Mendelian Randomization Study.

J Clin Endocrinol Metab 2020 07;105(7)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Context: Little is known about the association between haptoglobin level and cardiometabolic traits. A previous genome-wide association study identified rs2000999 in the HP gene as the stronger genetic contributor to serum haptoglobin level in European populations.

Objective And Design: We investigated the association of HP rs2000999 with serum haptoglobin and childhood and adult obesity in up to 540/697 and 592/691 Mexican cases and controls, respectively. Anthropometric and biochemical data were collected. Serum haptoglobin was measured by an immunoturbidimetry assay. HP rs2000999 was genotyped using the TaqMan technology. Mendelian randomization analysis was performed using the Wald and inverse variance weighting methods.

Results: Haptoglobin level was positively associated with childhood and adult obesity. HP rs2000999 G allele was positively associated with haptoglobin level in children and adults. HP rs2000999 G allele was positively associated with childhood but not adult obesity. The association between HP rs2000999 and childhood obesity was removed after adjusting for haptoglobin level. In a Mendelian randomization analysis, haptoglobin level genetically predicted by HP rs2000999 showed a significant causal effect on childhood obesity by the Wald and inverse variance weighting methods.

Conclusion: Our data provide evidence for the first time for a causal positive association between serum haptoglobin level and childhood obesity in the Mexican population. Our study contributes to the genetic elucidation of childhood obesity and proposes haptoglobin as an important biomarker and treatment target for obesity.
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http://dx.doi.org/10.1210/clinem/dgaa213DOI Listing
July 2020

Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children.

Clin Chem Lab Med 2020 10;58(11):1819-1827

Research Unit EA_1122; IGE-PCV - Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire, Université de Lorraine, Faculté de Pharmacie, Nancy, France.

Background Growing evidence reports an association between inflammatory markers, obesity and blood pressure (BP). Specifically, the intergenic single nucleotide polymorphism (SNP) rs7556897T > C (MAF = 0.34) located between SLC19A3 and the CCL20 was shown to be associated with chronic inflammatory diseases. In addition, CCL20 expression was found increased in pancreatic islets of obese rodents and human pancreatic β cells under the influence of inflammation. In this study, we hypothesized that SNP rs7556897 could affect BP levels, thus providing a link between inflammation, BP and obesity. Methods BP was measured under supine position with a manual sphygmomanometer; values reported were the means of three readings. We analyzed rs7556897 in 577 normal weight and 689 obese French children. Using real-time polymerase chain reaction (PCR), we quantified CCL20 and SLC19A3 expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) of normal weight and overweight children. Results The rs7556897C allele was negatively associated with diastolic BP in normal weight children (β = -0.012 ± 0.004, p = 0.006) but positively associated in obese children (β = 2.178 ± 0.71, p = 0.002). A significant interaction between rs7556897T > C and the obesity status (obese or normal weight) was detected (β = 3.49, p = 9.79 × 10-5) for BP in a combined population analysis. CCL20 mRNA was only expressed in the adipose tissue of overweight children, and its expression levels were 10.7×  higher in PBMCs of overweight children than normal weight children. Finally, CCL20 mRNA levels were positively associated with rs7556897T > C in PBMCs of 58 normal weight children (β = 0.43, p = 0.002). SLC19A3 was not expressed in PBMCs, and in adipose tissue, it showed same levels of expression in normal weight and overweight children. The gene expression results may highlight a specific involvement of CCL20 via communicating obesity/inflammation pathways that regulate BP. Conclusions Childhood obesity reverses the effect of rs7556897T > C on diastolic BP, possibly via the modulation of CCL20 expression levels.
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http://dx.doi.org/10.1515/cclm-2019-0292DOI Listing
October 2020

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Context: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear.

Objective And Design: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults.

Results: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population.

Conclusion: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.
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http://dx.doi.org/10.1210/clinem/dgz276DOI Listing
April 2020

Deficits in executive function and suppression of default mode network in obesity.

Neuroimage Clin 2019 26;24:102015. Epub 2019 Oct 26.

Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario, Canada; Peter Boris Centre for Addictions Research, McMaster University & St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada. Electronic address:

Background: Although nutritional and metabolic factors are well established in obesity, neurocognitive determinants are less understood. Using data from the Human Connectome Project, this study concurrently investigated neurocognitive performance, neural activation during a working memory task, and cortical brain morphometry in relation to obesity in a group of young adults, 22-35 years old.

Methods: Using a case-control design, obese individuals (n = 243, body mass index [BMI] ≥ 30 kg/m) were compared to a control group of lean BMI individuals (n = 469, BMI = 18-24.9 kg/m). Performance tests comprised a battery of behavioral neurocognitive assessments. Neural activity was measured as blood-oxygenation-level-dependent (BOLD) activity during an N-Back task using functional magnetic resonance imaging (fMRI). Cortical morphometry included indices of volume, thickness, and surface area.

Results: Relative to the control group, the obese group exhibited significantly worse performance in terms of the National Institutes of Health Toolkit (NIH) 9-Hole Peg Board, Penn Working Memory Test, Delay Discounting, Penn Progressive Matrices, NIH Picture Vocabulary Test, Dimensional Change Card Sort Test and the in-scanner N-Back working memory test (FDR-corrected ps<0.05; ds = 0.231-0.405). The obese group also exhibited significantly greater BOLD activation in N-Back task-negative regions, including the ventromedial prefrontal cortex, posterior cingulate, and right precentral gyrus (FDR-corrected ps<0.05). Supplemental functional connectivity analyses provided evidence that the implicated regions were part of the default mode network. Significant differences in morphometry were present in the medial orbitofrontal cortex, rostral anterior cingulate cortex, inferior and superior parietal gyri, and temporal pole (FDR-corrected p<0.001). A data-driven integrative model classified 73.8% of participants correctly.

Conclusions And Relevance: This multimodal investigation suggests diverse aspects of neurocognition are associated with obesity, particularly implicating deficits in executive function and ineffective suppression of the default mode network.
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http://dx.doi.org/10.1016/j.nicl.2019.102015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861638PMC
September 2020

Association between impulsivity traits and body mass index at the observational and genetic epidemiology level.

Sci Rep 2019 11 26;9(1):17583. Epub 2019 Nov 26.

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, United States of America.

We investigated the association between impulsivity related traits and BMI at the observational and genetic epidemiology level in a cross-sectional population of healthy young American-European adults. We studied 998 students and university staff of European ancestry recruited from Chicago (Illinois) and Athens (Georgia). We measured 14 impulsivity variables using three broad categories: impulsive choice, action and personality. Weight and height of participants were measured by research assistants. The single-nucleotide polymorphism (SNP) rs3751812 in the fat mass and obesity-associated (FTO) gene was genotyped using the Illumina PsychArray BeadChip platform. Within the three broad domains of impulsivity, 4 parameters (delay discounting of rewards area under the curve and average of k indexes, Conner's continuous performance test, and negative urgency) were associated with BMI. The FTO rs3751812 minor allele T was associated with higher BMI. Of the 14 impulsivity variables, rs3751812 T was associated with more premeditation and perseverance, before and after adjusting for BMI. The association between FTO rs3751812 and BMI adjusted for premeditation remained significant, but disappeared after adjusting for perseverance and for both perseverance and premeditation traits. Our observational and genetic data indicate a complex pattern of association between impulsive behaviors and BMI in healthy young American-European adults.
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http://dx.doi.org/10.1038/s41598-019-53922-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879509PMC
November 2019

Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

Sci Rep 2019 11 20;9(1):17123. Epub 2019 Nov 20.

Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.
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http://dx.doi.org/10.1038/s41598-019-53388-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868229PMC
November 2019

Summer Season and Recommended Vitamin D Intake Support Adequate Vitamin D Status throughout Pregnancy in Healthy Canadian Women and Their Newborns.

J Nutr 2020 04;150(4):739-746

School of Kinesiology, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, Children's Health Research Institute, Western University, London, Ontario, Canada.

Background: Vitamin D deficiency in pregnancy is reported as a prevalent public health problem.

Objectives: We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D.

Methods: Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured.

Results: Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (<30 nmol/L) occurred. Serum 1,25(OH)2D concentrations were significantly higher in late pregnancy (101.1 ± 26.9 pmol/L) than in early pregnancy (82.2 ± 19.2 pmol/L, P < 0.001, n = 84). Cord serum 25(OH)D concentrations averaged 55% of maternal concentrations. In adjusted multivariate analyses, maternal vitamin D status in early pregnancy was positively associated with summer season (est.β: 13.07; 95% CI: 5.46, 20.69; P < 0.001) and supplement intake (est.β: 0.01; 95% CI: 0.00, 0.01; P < 0.001); and in late pregnancy with summer season (est.β: 24.4; 95% CI: 15.6, 33.2; P < 0.001), nonmilk dairy intake (est.β: 0.17; 95% CI: 0.02, 0.32; P = 0.029), and supplement intake (est.β: 0.01; 95% CI: 0.00, 0.01; P = 0.04).

Conclusions: Summer season and recommended vitamin D intakes supported adequate vitamin D status throughout pregnancy and in cord blood at >50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.
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http://dx.doi.org/10.1093/jn/nxz276DOI Listing
April 2020

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Hum Mol Genet 2019 10;28(19):3327-3338

Unidad de Investigacion Medica en Bioquımica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.
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http://dx.doi.org/10.1093/hmg/ddz161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859434PMC
October 2019

Zinc Supplementation and Body Weight: A Systematic Review and Dose-Response Meta-analysis of Randomized Controlled Trials.

Adv Nutr 2020 03;11(2):398-411

Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose-response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose-response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I2 = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = -0.55 kg; 95% CI: -1.06, -0.04 kg; P = 0.03; I2 = 31.5%). Dose-response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.
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http://dx.doi.org/10.1093/advances/nmz084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442320PMC
March 2020

Loss-of-function mutations in the melanocortin-3 receptor gene confer risk for human obesity: A systematic review and meta-analysis.

Obes Rev 2019 08 14;20(8):1085-1092. Epub 2019 May 14.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

The association between rare coding loss-of-function (LOF) mutations in the melanocortin receptor 3 (MC3R) gene and human obesity is controversial. To fill this gap of knowledge, we performed a systematic review and meta-analysis of genetic association studies in all ages and ethnicities. Two reviewers independently performed risk of bias assessment and extracted data. We searched Medline, Embase, Web of Science Core Collection, BIOSIS Preview, CINAHL, ProQuest Dissertations & Theses, and reference lists of relevant studies. All case-control, cross-sectional, prospective, and retrospective studies that evaluated prevalence of rare (less than 1% frequency) coding partial/complete LOF mutations in MC3R among individuals with obesity and normal weight were included. Our systematic search identified 1925 references relevant to the present review. Six studies were deemed eligible. Meta-analysis of 2969 individuals with obesity and 2572 with normal weight showed a positive association between rare heterozygous coding partial/complete LOF mutations in MC3R and obesity in children and adults of European, North African, and Asian ancestries (odds ratio = 3.07; 95% CI, 1.48-7.00; P = 4.2 × 10 ). Our data demonstrates that rare partial/complete LOF mutations in the coding region of MC3R confer three-time increased risk of obesity in humans, and implies that rare genetic variants with intermediate effects contribute to the missing heritability of obesity.
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http://dx.doi.org/10.1111/obr.12864DOI Listing
August 2019

Benefits and limitations of genome-wide association studies.

Nat Rev Genet 2019 08;20(8):467-484

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Genome-wide association studies (GWAS) involve testing genetic variants across the genomes of many individuals to identify genotype-phenotype associations. GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases. Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease. In this Review, we comprehensively assess the benefits and limitations of GWAS in human populations and discuss the relevance of performing more GWAS.
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http://dx.doi.org/10.1038/s41576-019-0127-1DOI Listing
August 2019
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