Publications by authors named "Rebecca Rohde"

27 Publications

  • Page 1 of 1

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

Pediatr Res 2021 Oct 13. Epub 2021 Oct 13.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors.

Methods: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling.

Results: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels.

Conclusions: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers.

Impact: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.
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http://dx.doi.org/10.1038/s41390-021-01729-7DOI Listing
October 2021

HPV Vaccination Is Safe-You Don't Have to Whisper It.

JAMA Netw Open 2021 Sep 1;4(9):e2125124. Epub 2021 Sep 1.

Department of Population Science and Policy, Southern Illinois University School of Medicine, Springfield.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.25124DOI Listing
September 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Survival outcomes for head and neck patients with Medicaid: A health insurance paradox.

Head Neck 2021 07 29;43(7):2136-2147. Epub 2021 Mar 29.

Department of Head and Neck Surgery & Communication Sciences, Duke University School of Medicine, Durham, North Carolina, USA.

Purpose: Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid.

Methods: A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality.

Results: Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured.

Conclusion: Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid.
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http://dx.doi.org/10.1002/hed.26682DOI Listing
July 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Epidermoid Cyst of the Buccal Space in a Pediatric Patient-A Rare Clinic Report.

Ear Nose Throat J 2021 Sep 24;100(5_suppl):525S-527S. Epub 2019 Nov 24.

Department of Otolaryngology-Head and Neck Surgery, 12274Saint Louis University School of Medicine, St Louis, MO, USA.

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http://dx.doi.org/10.1177/0145561319890694DOI Listing
September 2021

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

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

Effect of interpregnancy interval after a first pregnancy complicated by placental abruption, on adverse maternal and fetal outcomes in a second pregnancy.

J Matern Fetal Neonatal Med 2020 Nov 8;33(22):3809-3815. Epub 2019 Mar 8.

Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA.

For women who suffer from abruption in the first pregnancy, the extent to which birth spacing has an impact on maternal and fetal outcomes in a second pregnancy remains unclear. To examine the effect of interpregnancy interval (IPI) after a first pregnancy complicated by placental abruption, on adverse maternal and fetal outcomes in a subsequent pregnancy. This was a population-based retrospective cohort study using maternally-linked Missouri birth registry from 1989 to 2005 ( = 2069). Exposure of interest was IPI and outcomes were placental abruption, preeclampsia, preterm birth, small for gestational age, cesarean delivery, and neonatal plus fetal deaths (neofetal death) in a second pregnancy. Logistic regressions were used to assess the association between IPI and the outcomes. Compared with women with an IPI of 1-2 years, those with short IPI (<1 year) were more likely to experience preterm birth (aOR 3.01, 95% CI 1.71-5.28) and neonatal death (aOR 3.52, 95% CI 1.24-10.02) in their subsequent pregnancy. No significant associations between IPI and recurrent placental abruption or preeclampsia were detected. Women who become pregnant in less than a year's time of an initial placental abruption are at increased risk for preterm birth and neofetal death in a subsequent pregnancy. Other ischemic placental disease conditions are also shown to have serious health implications for a woman's next pregnancy.
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http://dx.doi.org/10.1080/14767058.2019.1586878DOI Listing
November 2020

Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.

Biol Psychiatry 2019 06 6;85(11):946-955. Epub 2018 Dec 6.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.

Methods: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.

Results: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.

Conclusions: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
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http://dx.doi.org/10.1016/j.biopsych.2018.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534468PMC
June 2019

Understanding of risk factors for the human papillomavirus (HPV) infection based on gender and race.

Sci Rep 2019 01 22;9(1):297. Epub 2019 Jan 22.

Harvard Medical School, The Massachusetts Eye and Ear Infirmary, Department of Otolaryngology, Boston, MA, 02114, USA.

This study assessed if race and gender predict known sexual risk factors associated with HPV. Data (n = 301) were from a cross-sectional study conducted at a drag racing event on September 12-13, 2015 in Madison, Illinois. Both multivariable logistic and linear regression models estimated the association between race, gender, and sexual risk factors. About 63% of participants were males, and 65% identified as Blacks. Compared to females, males were more likely to have a higher number of oral sexual partners (OR = 2.10; 95% CI: 1.23, 3.57). Males were also more likely to have earlier oral sexual (b = -2.10; 95% CI: -3.60, -0.60) and vaginal sexual (b = -1.10; 95% CI: -1.69, -0.31) debuts compared to females. Blacks were more likely to have higher number of vaginal sexual partners (OR = 3.38; 95% CI: 1.81, 6.31) and earlier vaginal sex (b = -1.09; 95% CI: -1.78, -0.41) but less likely to have earlier oral sexual debuts compared with Whites (b = 2.67; 95% CI: 1.21, -4.13). Because HPV is associated with several cancers, our findings provide impetus for the development of targeted educational interventions aimed at improving the knowledge of these sexual risk factors, especially among men and across race groups.
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http://dx.doi.org/10.1038/s41598-018-36638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342910PMC
January 2019

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Mol Psychiatry 2020 10 7;25(10):2392-2409. Epub 2019 Jan 7.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, Netherlands.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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http://dx.doi.org/10.1038/s41380-018-0313-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515840PMC
October 2020

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Am J Hum Genet 2019 01 27;104(1):112-138. Epub 2018 Dec 27.

School of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
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http://dx.doi.org/10.1016/j.ajhg.2018.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323610PMC
January 2019

Prevalence and sociodemographic factors associated with depression among hospitalized patients with head and neck cancer-Results from a national study.

Psychooncology 2018 12 4;27(12):2809-2814. Epub 2018 Oct 4.

Department of Epidemiology and Biostatistics, Saint Louis University College for Public Health and Social Justice, St Louis, Missouri.

Objective: Depression is a significant problem for patients with head and neck cancer (HNC). This study explored the prevalence of and sociodemographic and clinical factors associated with depression, among patients with HNC.

Methods: We performed a retrospective analysis of 71 541 cases of HNC using a national dataset, the Nationwide Inpatient Sample, from 2008 to 2013. Weighted, multivariate logistic regression analysis estimated association between sociodemographic/clinical factors and tumor anatomical site with diagnosis of a major depressive disorder.

Results: Overall prevalence of major depressive disorder in HNC was 9.3%; highest prevalence was found in patients with laryngeal cancer (28.5%). Compared with laryngeal cancer, there were lower odds of depression among patients with oral cavity cancer (adjusted odds ratio [aOR] = 0.90; 95% CI, 0.84-0.97) and other anatomic sites (aOR = 0.87; 95% CI, 0.81-0.94), except oropharyngeal cancer (aOR = 1.00; 95% CI, 0.93-1.08). For every unit increase in comorbidities, odds of depression increased by 20% (aOR = 1.20; 95% CI, 1.19-1.23). Sociodemographic factors associated with increased odds of depression included being female (aOR = 1.77; 95% CI, 1.68-1.87), white (aOR = 1.75; 95% CI, 1.59-1.92), and having Medicaid (aOR = 1.09; 95% CI, 1.01-1.19) or Medicare insurance (aOR = 1.19; 95% CI, 1.10-1.27).

Conclusions: Depression odds vary depending on HNC anatomic site, and one in four patients with laryngeal cancer may be depressed. Since depression is prevalent in this survivor cohort, it is important that psychosocial assessment and intervention are integrated into mainstream clinical care for patients with HNC.
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http://dx.doi.org/10.1002/pon.4893DOI Listing
December 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

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

Am J Respir Crit Care Med 2019 03;199(5):631-642

28 Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.

Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.

Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.

Methods: Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV, FVC, and FEV/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs.

Results: DPA and DHA were positively associated with FEV and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P = 9.4 × 10 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (P = 2.1 × 10; β = -161.0 ml), and the association was attenuated by higher DHA levels (P = 2.1 × 10; β = 36.2 ml).

Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.
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http://dx.doi.org/10.1164/rccm.201802-0304OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396866PMC
March 2019

An assessment of patient burdens from head and neck cancer survivorship care.

Oral Oncol 2018 07 21;82:115-121. Epub 2018 May 21.

Saint Louis University, Department of Otolaryngology - Head and Neck Surgery, Saint Louis, MO, United States. Electronic address:

Objectives: To assess head and neck cancer (HNC) patients' perspectives on the value and burdens of routine cancer follow-up care.

Materials And Methods: Data was obtained from HNC patients (n = 100) at an urban, tertiary head and neck cancer clinic. A novel 15-question survey tool evaluated the logistic, financial, and psychosocial burdens associated with clinic visits. The clinical characteristics and survey responses of demographic groups were analyzed with comparative statistics. Linear regression modeling was utilized to identify predictors of overall stress.

Results: A majority of study participants were male (74%), white (83%), and had histories of tobacco (77%) and alcohol (77%) use. Most participants were satisfied with the frequency of their office visits (75%). Patients with laryngeal cancer, advanced stage disease, or who underwent multimodality therapy more often desired increased appointment frequency. These patients also rated the burdens of travel cost and overall stress higher, compared to patients desiring visits less often (41.5% vs 28.4%, p = 0.047 and 46.6% vs 38.3%, p = 0.003, respectively). Travel stress was associated with highest overall stress (beta 0.6, CI: 0.4, 0.7).

Conclusion: The HNC survivor population is uniquely disenfranchised in several social and economic ways. While most patients are satisfied with their follow-up care, a significant subset of patients - those with limited social support, high financial stress, functional deficits, and those with transportation burdens - desire more frequent care. Survivorship care plans should incorporate the perspectives of current survivors.
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http://dx.doi.org/10.1016/j.oraloncology.2018.04.024DOI Listing
July 2018

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

Vaccine 2018 06 9;36(25):3629-3634. Epub 2018 May 9.

Saint Louis University College of Public Health and Social Justice, Department of Epidemiology, St. Louis, MO 63104, USA; Saint Louis University Cancer Center, St. Louis, MO 63104, USA; Saint Louis University, Department of Otolaryngology-Head and Neck Surgery, St. Louis, MO 63104, USA. Electronic address:

Objectives: There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population.

Materials And Methods: Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion.

Results: A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion.

Conclusion: HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile.
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http://dx.doi.org/10.1016/j.vaccine.2018.05.022DOI Listing
June 2018

Correlates of human papillomavirus (HPV) vaccination initiation and completion among 18-26 year olds in the United States.

Hum Vaccin Immunother 2018 1;14(8):2016-2024. Epub 2018 Jun 1.

c Department of Epidemiology , College for Public Health and Social Justice, Saint Louis University , Saint Louis , MO , USA.

Purpose: To examine correlates of HPV vaccination uptake in a nationally representative sample of 18-26-year-old adults.

Methods: Young adults aged 18-26 years were identified from the 2014 and 2015 National Health Interview Survey (n = 7588). Survey-weighted multivariable logistic regression models estimated sociodemographic factors associated with HPV vaccine initiation (≥1 dose) and completion (≥3 doses).

Results: Approximately 27% of study participants had initiated the HPV vaccine and 16% had completed the HPV vaccine. Participants were less likely to initiate the vaccine if they were men [(adjusted odds ratio) 0.19; (95% confidence interval) 0.16-0.23], had a high school diploma (0.40; 0.31-0.52) or less (0.46; 0.32-0.64) vs. college graduates, and were born outside the United States (0.52; 0.40-0.69). But, participants were more likely to initiate the HPV vaccine if they visited the doctor's office 1-5 times (2.09; 1.56-2.81), or ≥ 6 times (1.86; 1.48-2.34) within the last 12 months vs. no visits. Odds of completing HPV vaccine uptake followed the same pattern as initiation. And after stratifying the study population by gender and foreign-born status, these variables remained statistically significant.

Conclusions: In our nationally representative study, only one out of six 18-26 year olds completed the required vaccine doses. Men, individuals with high school or less education, and those born outside the United States were less likely to initiate and complete the HPV vaccination. Our findings suggest that it may be useful to develop targeted interventions to promote HPV vaccination among those in the catch-up age range.
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http://dx.doi.org/10.1080/21645515.2018.1467203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150015PMC
April 2019

External Auditory Canal Foreign Body Extraction Outcomes.

Ann Otol Rhinol Laryngol 2017 Nov 28;126(11):755-761. Epub 2017 Sep 28.

1 Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, St. Louis Missouri, USA.

Objectives: To compare pediatric external auditory canal (EAC) foreign body extraction outcomes by clinical setting and identify factors predictive of successful removal.

Methods: Retrospective review of pediatric patients with EAC foreign bodies to a single institution emergency department (ED) and otolaryngology clinic (OTO) between January 2010 and April 2015. Patient characteristics, foreign body type, removal attempts, instrumentation utilized, and complications were evaluated with respect to clinical setting and patient outcome.

Results: In all, 1197 patients with EAC foreign bodies were identified, 759 (63%) of whom presented primarily to the ED. Successful removal was achieved in OTO in 92.9% of cases and the ED in 67.9% of cases. Beads and spherical objects had the overall lowest rates of successful removal. Likelihood of removal decreased significantly after one unsuccessful attempt. Complications were reported in 35.7% of patients undergoing removal in the ED and 5.0% of patients undergoing removal in the otolaryngology clinic.

Conclusions: Patients commonly present to the ED for removal of EAC foreign bodies. Referral to an otolaryngologist is recommended if the object is spherical or after one unsuccessful attempt at removal.
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http://dx.doi.org/10.1177/0003489417731578DOI Listing
November 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

Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium.

Diabetologia 2017 12 13;60(12):2384-2398. Epub 2017 Sep 13.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

Aims/hypothesis: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies.

Methods: A multiethnic study of up to 26,760 unrelated individuals without diabetes, of predominantly Hispanic/Latino and African ancestries, were genotyped using the Metabochip. Transethnic meta-analysis of racial/ethnic-specific linear regression analyses were performed for fasting glucose and fasting insulin. We attempted to replicate 39 fasting glucose and 17 fasting insulin loci. Genetic fine-mapping was performed through sequential conditional analyses in 15 regions that included both the initially reported SNP association(s) and denser coverage of SNP markers. In addition, Metabochip-wide analyses were performed to discover novel fasting glucose and fasting insulin loci. The most significant SNP associations were further examined using bioinformatic functional annotation.

Results: Previously reported SNP associations were significantly replicated (p ≤ 0.05) in 31/39 fasting glucose loci and 14/17 fasting insulin loci. Eleven glycaemic trait loci were refined to a smaller list of potentially causal variants through transethnic meta-analysis. Stepwise conditional analysis identified two loci with independent secondary signals (G6PC2-rs477224 and GCK-rs2908290), which had not previously been reported. Population-specific conditional analyses identified an independent signal in G6PC2 tagged by the rare variant rs77719485 in African ancestry. Further Metabochip-wide analysis uncovered one novel fasting insulin locus at SLC17A2-rs75862513.

Conclusions/interpretation: These findings suggest that while glycaemic trait loci often have generalisable effects across the studied populations, transethnic genetic studies help to prioritise likely functional SNPs, identify novel associations that may be population-specific and in turn have the potential to influence screening efforts or therapeutic discoveries.

Data Availability: The summary statistics from each of the ancestry-specific and transethnic (combined ancestry) results can be found under the PAGE study on dbGaP here: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1.
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http://dx.doi.org/10.1007/s00125-017-4405-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918310PMC
December 2017

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

PLoS Genet 2017 Apr 21;13(4):e1006719. Epub 2017 Apr 21.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, United States of America.

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.
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http://dx.doi.org/10.1371/journal.pgen.1006719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419579PMC
April 2017

A Congenital Nasal Mass Causing Respiratory Distress.

JAMA Otolaryngol Head Neck Surg 2017 04;143(4):417-418

Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, St Louis, Missouri.

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http://dx.doi.org/10.1001/jamaoto.2016.2974DOI Listing
April 2017

Pleiotropic genes for metabolic syndrome and inflammation.

Mol Genet Metab 2014 Aug 9;112(4):317-38. Epub 2014 May 9.

Department of Health Studies, University of Chicago, IL, USA. Electronic address:

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation.
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http://dx.doi.org/10.1016/j.ymgme.2014.04.007DOI Listing
August 2014

Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study.

BMC Med Genet 2013 Jan 11;14. Epub 2013 Jan 11.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

Background: Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.

Methods: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE)' Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses.

Results: We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, p(interaction) = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5 x 10(-5)), vs. former/never smokers (β = 0.006, p = 0.05, p(interaction) = 0.08).

Conclusions: These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results.

Clinical Trial Registration: NCT00000611.
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http://dx.doi.org/10.1186/1471-2350-14-6DOI Listing
January 2013
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