Publications by authors named "Alexis C Frazier-Wood"

59 Publications

Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis.

BMJ 2019 07 25;366:l4292. Epub 2019 Jul 25.

Objective: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.

Design: Individual participant data meta-analysis.

Data Sources: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.

Review Methods: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.

Results: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I=7.1%, τ=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I=18.0%, τ=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I=58.8%, τ=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I=25.9%, τ=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.

Conclusions: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
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http://dx.doi.org/10.1136/bmj.l4292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652797PMC
July 2019

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

PLoS Genet 2019 04 16;15(4):e1007739. Epub 2019 Apr 16.

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
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http://dx.doi.org/10.1371/journal.pgen.1007739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467367PMC
April 2019

An Exome-Wide Sequencing Study of the GOLDN Cohort Reveals Novel Associations of Coding Variants and Fasting Plasma Lipids.

Front Genet 2019 26;10:158. Epub 2019 Feb 26.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United States.

Associations of both common and rare genetic variants with fasting blood lipids have been extensively studied. However, most of the rare coding variants associated with lipids are population-specific, and exploration of genetic data from diverse population samples may enhance the identification of novel associations with rare variants. We searched for novel coding genetic variants associated with fasting lipid levels in 894 samples from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) with exome-wide sequencing-based genotype data. In single variant tests, one variant (rs11171663 in ) was associated with fasting triglyceride levels ( = 7.66E-08), explaining approximately 3.2% of the total trait variance. In gene-based tests, we found statistically significant associations between ( = 1.77E-07) and ( = 7.18E-07) and triglycerides, as well as between ( = 3.00E-07) and low-density lipoprotein cholesterol. In another independent replication cohort consisting of 3,183 African American samples from Hypertension Genetic Epidemiology Network (HyperGEN) and the Genetic Epidemiology Network of Arteriopathy (GENOA), the top genes achieved -values of 0.04 (), 0.08 (), and 0.02 (). In GOLDN, gene transcript levels of and were associated with fasting triglycerides ( = 0.07 and = 0.02), highlighting functional relevance of our findings. In this study, we present preliminary evidence of novel rare variant determinants of fasting lipids, and reveal potential underlying molecular mechanisms. Moreover, these results were replicated in an independent cohort. Our findings may inform novel biomarkers of disease risk and treatment targets.
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http://dx.doi.org/10.3389/fgene.2019.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399202PMC
February 2019

Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med 2018 10 10;15(10):e1002670. Epub 2018 Oct 10.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Background: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).

Methods And Findings: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.

Conclusions: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1002670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179183PMC
October 2018

Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function.

Br J Nutr 2018 11 12;120(10):1159-1170. Epub 2018 Sep 12.

7Center for Public Health Genomics,University of Virginia School of Medicine,Charlottesville,VA 22903,USA.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
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http://dx.doi.org/10.1017/S0007114518002180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263170PMC
November 2018

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium.

Mol Psychiatry 2019 12 9;24(12):1920-1932. Epub 2018 Jul 9.

Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
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http://dx.doi.org/10.1038/s41380-018-0079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326896PMC
December 2019

Factors of health in the protection against death and cardiovascular disease among adults with subclinical atherosclerosis.

Am Heart J 2018 04 11;198:180-188. Epub 2017 Nov 11.

Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Background: Although cardiovascular disease (CVD) prevention traditionally emphasizes risk factor control, recent evidence also supports the promotion of "health factors" associated with cardiovascular wellness. However, whether such health factors exist among adults with advanced subclinical atherosclerosis is unknown. We aimed to study the association between health factors and events among persons with elevated coronary artery calcium (CAC).

Methods: Self-reported health-factors studied included nonsmoking, physical activity, Mediterranean-style diet, sleep quality, emotional support, low stress burden, and absence of depression. Measured health-factors included optimal weight, blood pressure, lipids, and glucose. Multivariable-adjusted Cox models examined the association between health factors and incident CVD or mortality, independent of risk factor treatment. Accelerated failure time models assessed whether health factors were associated with relative time delays in disease onset.

Results: Among 1,601 Multi-Ethnic Study of Atherosclerosis participants with CAC >100 without baseline clinical atherosclerotic CVD, mean age was 69 (±9) years, 64% were male, and median CAC score was 332 Agatston units. Over 12 years of follow-up, nonsmoking, high-density lipoprotein cholesterol levels >40 mg/dL for men and >50 mg/dL for women, and low stress burden were inversely associated with ASCVD (hazard ratios ranging from 0.58 to 0.71, all P<.05). Nonsmoking, glucose levels <100 mg/dL, regular physical activity, and low stress burden were inversely associated with mortality (hazard ratios ranging from 0.40 to 0.77, all P<.05). Each of these factors was also associated with delays in onset of clinical disease, as was absence of depression.

Conclusions: Adults with elevated CAC appear to have healthy lifestyle options to lower risk and delay onset of CVD, over and above standard preventive therapies.
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http://dx.doi.org/10.1016/j.ahj.2017.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901883PMC
April 2018

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort.

J Lipid Res 2018 04 20;59(4):722-729. Epub 2018 Feb 20.

School of Biomedical Informatics The University of Texas Health Science Center at Houston, Houston, TX 77030; School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030. Electronic address:

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in , , and are significantly associated with fasting LDL cholesterol response to FFB ( = 1.24E-07), triglyceride postprandial area under the increase (AUI) ( = 2.31E-06), and triglyceride postprandial AUI response to FFB ( = 1.88E-06), respectively. We sought to replicate the association for in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of is associated with triglyceride postprandial AUI ( < 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.
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http://dx.doi.org/10.1194/jlr.P080333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880495PMC
April 2018

Drawing conclusions from within-group comparisons and selected subsets of data leads to unsubstantiated conclusions: Letter regarding Malakellis et al.

Aust N Z J Public Health 2018 04 27;42(2):214. Epub 2017 Dec 27.

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University - Bloomington, US.

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http://dx.doi.org/10.1111/1753-6405.12755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891379PMC
April 2018

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis.

Diabetologia 2018 02 2;61(2):317-330. Epub 2017 Nov 2.

Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.

Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits.

Methods: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway.

Results: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10) and higher fasting insulin (0.030 ± 0.005 [log pmol/l], p = 2.0 × 10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 log pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant.

Conclusions/interpretation: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis.

Trial Registration: Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses' Health Study).
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http://dx.doi.org/10.1007/s00125-017-4475-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826559PMC
February 2018

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Am J Respir Cell Mol Biol 2018 03;58(3):391-401

30 School of Public Health, University of Adelaide, Adelaide, South Australia, Australia.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
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http://dx.doi.org/10.1165/rcmb.2017-0237OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854957PMC
March 2018

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies.

Lancet Diabetes Endocrinol 2017 12 12;5(12):965-974. Epub 2017 Oct 12.

US Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Houston, TX, USA.

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.

Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.

Findings: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I=53·9%, p=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I=63·0%, p<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p≥0·13).

Interpretation: Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.

Funding: Funders are shown in the appendix.
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http://dx.doi.org/10.1016/S2213-8587(17)30307-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029721PMC
December 2017

Coffee consumption is not associated with prevalent subclinical cardiovascular disease (CVD) or the risk of CVD events, in nonalcoholic fatty liver disease: results from the multi-ethnic study of atherosclerosis.

Metabolism 2017 10 24;75:1-5. Epub 2017 Jun 24.

Los Angeles Biomedical Research Institute, Division of Cardiology, Harbor-UCLA Medical Center, Los Angeles, CA, United States. Electronic address:

Background: Atherosclerosis and its clinical sequelae represent the leading cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). While epidemiologic data support the hepatoprotective benefits of coffee in NAFLD, whether coffee improves NAFLD-associated CVD risk is unknown.

Methods: We examined 3710 ethnically-diverse participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, without history of known liver disease, and with available coffee data from a validated 120-item food frequency questionnaire. All participants underwent baseline non-contrast cardiac CT from which NAFLD was defined by liver:spleen ratio (L:S<1.0), and subclinical CVD was defined by coronary artery calcium (CAC)>0. Major CVD events were defined by the first occurrence of myocardial infarction, cardiac arrest, angina, stroke, or CVD death. We used log-binomial regression to calculate the adjusted prevalence ratio (PR) for CAC>0 by coffee intake and NAFLD status, and events were compared between groups using frequency of events within adjusted Cox proportional hazard regression models.

Results: Seventeen percent (N=637) of participants met criteria for NAFLD. NAFLD participants were more likely to have elevated BMI (mean 31.1±5.5kg/m vs. 28.0±5.2kg/m, p<0.0001), and diabetes (22% vs. 11%, p<0.0001), but did not differ in daily coffee consumption (p=0.97). Among NAFLD participants, coffee consumption was not associated with prevalent, baseline CAC>0 (PR=1.02 [0.98-1.07]). Over 12.8years of follow-up, 93 NAFLD and 415 non-NAFLD participants experienced a CV event. However, coffee intake was not associated with incident CVD events, in either NAFLD (HR=1.05 [0.91-1.21]) or non-NAFLD participants (HR=1.03 [0.97-1.11]).

Conclusion: In a large, population-based cohort, coffee consumption was not associated with the prevalence of subclinical CVD, nor did coffee impact the future risk of major CVD events, regardless of underlying NAFLD status.
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http://dx.doi.org/10.1016/j.metabol.2017.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657519PMC
October 2017

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.

Mol Nutr Food Res 2018 02 11;62(3). Epub 2017 Dec 11.

Department of Clinical Chemistry, Fimlab Laboratories, Tampere University School of Medicine, Tampere, Finland.

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.

Methods And Results: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10 , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10 such that each serving of low-fat dairy was associated with 0.225 kg m lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure.

Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
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http://dx.doi.org/10.1002/mnfr.201700347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803424PMC
February 2018

Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic.

Open Heart 2017;4(1):e000550. Epub 2017 Apr 28.

Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.

Objective: Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are preventive against cardiovascular disease (CVD) and several cancer types, but long-term use has been associated with significant health risks, resulting in conflicting recommendations on NSAID use for prevention of CVD and cancer. Previous research indicates that aspirin use increases with age and CVD risk factors and that a large percentage of the US population regularly use analgesics, including NSAIDs, but there has not been a recent, in-depth assessment of NSAID use prevalence, changes in use over time or predictors of NSAID use in the USA.

Methods: We used the cross-sectional, National Health And Nutrition Examination Survey (NHANES) from 1988 to 1994 and three continuous cycles (1999-2004) to assess regular NSAID use prevalence, changes over time and predictors of regular NSAID use.

Results: Overall, regular NSAID use increased over time and varied by demographic features. Participants over 60 years of age, women, participants with high body mass index, increased waist circumference or heart disease were significantly more likely to be regular NSAID users. By contrast, non-Hispanic African American and Mexican American participants were significantly less likely to regularly use NSAIDs.

Conclusions: This study uses a nationally representative data set (NHANES) to provide an exploration of regular NSAID use patterns over time, highlighting several demographic, lifestyle and clinical conditions associated with regular NSAID use. Understanding who is likely to regularly use NSAIDs enables more targeted messaging both for increasing the preventive benefits and for limiting the toxicities associated with regular use of NSAIDs.
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http://dx.doi.org/10.1136/openhrt-2016-000550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471872PMC
April 2017

Activity level in the lab: Overlap with shyness indicates it is more than pure motoric activity.

Dev Psychol 2017 09 29;53(9):1611-1619. Epub 2017 Jun 29.

Department of Psychological & Brain Sciences, Boston University.

The observation that children's activity level (AL) differs between novel and familiar situations is well established. What influences individual differences in how AL is different across these situations is less well understood. Drawing on animal literature, which links rats' AL when 1st placed in a novel setting with novelty seeking phenotypes, and child temperament literature, which links AL, novelty response, and shyness, we hypothesized that shyness would be an important component of children's AL in a novel situation. We examined this using mechanically assessed AL from 2 situations (the home and the lab) and 2 measures of shyness (1 parent-rated and 1 observer-rated) on up to 313 twin pairs (145 monozygotic and 168 dizygotic), at 2 and 3 years of age. Biometric genetic models removed from lab AL the variance shared with home AL, representing what was different in AL when the child entered the lab compared to the home. We report that almost half (43%) of the genetic component of AL in the lab was independent of AL in the home, and this unique genetic component shared genetic covariance with shyness. Shyness influences AL in a novel situation such as the lab, indicating that mechanically assessed AL represents more than global motoric activity and provides information on a child's temperamental response to novelty. (PsycINFO Database Record
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http://dx.doi.org/10.1037/dev0000348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565700PMC
September 2017

Evaluation of diet pattern and weight gain in postmenopausal women enrolled in the Women's Health Initiative Observational Study.

Br J Nutr 2017 Apr 16;117(8):1189-1197. Epub 2017 May 16.

11Children's Nutrition Research Center,Baylor College of Medicine,Room CNRC-2036,Mail Stop BCM320, Houston,TX 77030,USA.

It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49-81 years (mean 63·6 (sd 7·4) years) from the Women's Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture's Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.
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http://dx.doi.org/10.1017/S0007114517000952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728369PMC
April 2017

Genetic associations with lipoprotein subfraction measures differ by ethnicity in the multi-ethnic study of atherosclerosis (MESA).

Hum Genet 2017 06 28;136(6):715-726. Epub 2017 Mar 28.

Department of Pediatrics, USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, 77030, USA.

A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European-Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African-Americans (AAs), 1450 Hispanic-Americans (HAs), and 775 Chinese-Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study center, and genetic ancestry (based on principal components), and additionally adjusted for Mexican/Non-Mexican status in HAs. A false discovery rate correction was applied separately within the results for each ethnicity to correct for multiple testing. Power calculations revealed that we did not have the power for SNP-based measures of association, so we analyzed phenotype-specific genetic risk scores (GRSs), constructed as in the original genome-wide analysis. We successfully replicated all 15 GRS-lipoprotein associations in 2527 EAs. Among the 15 significant GRS-lipoprotein associations in EAs, 11 were significant in AAs, 13 in HAs, and 1 in CHNs. Further analyses revealed that ethnicity differences could not be explained by differences in linkage disequilibrium, lipid lowering drugs, diabetes, or gender. Our study emphasizes the importance of ethnicity (here indexing genetic ancestry) in genetic risk for CVD and highlights the need to identify ethnicity-specific genetic variants associated with CVD risk.
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http://dx.doi.org/10.1007/s00439-017-1782-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429342PMC
June 2017

Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations.

J Lipid Res 2017 05 15;58(5):974-981. Epub 2017 Mar 15.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN.

MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at and [log(Bayes factor) ≥ 8.07] and for gondoic acid at and [log(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at and loci. The greatest improvement was observed at , where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of , , , and with palmitoleic acid and of and with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.
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http://dx.doi.org/10.1194/jlr.P071860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408616PMC
May 2017

Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level.

Hum Mol Genet 2016 12;25(23):5244-5253

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.

Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its genetic contribution has never been studied. Our recent study suggests nocturnal SaO2 is heritable. We performed linkage analysis, association analysis and haplotype analysis of average nocturnal oxyhaemoglobin saturation in participants in the Cleveland Family Study (CFS), followed by gene-based association and additional tests in four independent samples. Linkage analysis identified a peak (LOD = 4.29) on chromosome 8p23. Follow-up association analysis identified two haplotypes in angiopoietin-2 (ANGPT2) that significantly contributed to the variation of SaO2 (P = 8 × 10-5) and accounted for a portion of the linkage evidence. Gene-based association analysis replicated the association of ANGPT2 and nocturnal SaO2. A rare missense SNP rs200291021 in ANGPT2 was associated with serum angiopoietin-2 level (P = 1.29 × 10-4), which was associated with SaO2 (P = 0.002). Our study provides the first evidence for the association of ANGPT2, a gene previously implicated in acute lung injury syndromes, with nocturnal SaO2, suggesting that this gene has a broad range of effects on gas exchange, including influencing oxygenation during sleep.
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http://dx.doi.org/10.1093/hmg/ddw324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078634PMC
December 2016

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

Am J Med 2017 02 15;130(2):188-197.e5. Epub 2016 Sep 15.

Division of Cardiology, Department of Medicine, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Md.

Background: Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain.

Methods: We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events.

Results: Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression.

Conclusions: Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake.
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http://dx.doi.org/10.1016/j.amjmed.2016.08.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263166PMC
February 2017

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

JAMA Intern Med 2016 08;176(8):1155-66

Department of Odontology, Umeå University, Umeå, Sweden.

Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.

Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.

Data Sources: A global consortium of 19 studies identified by November 2014.

Study Selection: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD.

Data Extraction And Synthesis: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes.

Main Outcomes And Measures: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI).

Results: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses.

Conclusions And Relevance: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.
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http://dx.doi.org/10.1001/jamainternmed.2016.2925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183535PMC
August 2016

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

Nat Genet 2016 06 18;48(6):624-33. Epub 2016 Apr 18.

Max Planck Institute for Human Development, Berlin, Germany.

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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http://dx.doi.org/10.1038/ng.3552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884152PMC
June 2016

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.

Am J Respir Crit Care Med 2016 Oct;194(7):886-897

10 Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas.

Rationale: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.

Objectives: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.

Methods: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.

Measurements And Main Results: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility.

Conclusions: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.
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http://dx.doi.org/10.1164/rccm.201512-2431OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074655PMC
October 2016

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis.

PLoS One 2016 12;11(2):e0149267. Epub 2016 Feb 12.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States of America.

Background: Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults.

Methods And Findings: Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake.

Conclusion: Absence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149267PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752232PMC
July 2016

Satiety and the Self-Regulation of Food Take in Children: a Potential Role for Gene-Environment Interplay.

Curr Obes Rep 2016 Mar;5(1):81-7

USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX, 77030, USA.

Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity.
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http://dx.doi.org/10.1007/s13679-016-0194-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798905PMC
March 2016