Dataset Information

Genetic associations with metabolic syndrome and its quantitative traits by race/ethnicity in the United States.

ABSTRACT: Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample.We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ethnicity.Risk allele frequencies varied by race/ethnicity for all eight loci (P<0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P>0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P>0.05).The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability.

SUBMITTER: Vassy JL

PROVIDER: S-EPMC3225057 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Genetic associations with metabolic syndrome and its quantitative traits by race/ethnicity in the United States.

Vassy Jason L JL Shrader Peter P Yang Quanhe Q Liu Tiebin T Yesupriya Ajay A Chang Man-Huei MH Dowling Nicole F NF Ned Renée M RM Dupuis Josée J Florez Jose C JC Khoury Muin J MJ Meigs James B JB

Metabolic syndrome and related disorders 20110817 6

<h4>Background</h4>Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample.<h4>Methods</h4>We compared the risk allele frequencies of eight SNPs previously as ...[more]

PMID: 21848424

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Project description:BackgroundNational social determinant of health (SDoH) studies on gastrointestinal cancers (GIC) have observed single GIC-types for surgery but not across all GIC-types, non-surgical treatments outcomes, or mortality. The Social Vulnerability Index (SVI), a validated large-data SDoH-tool, quantifiably characterizes the interrelatedness of SDoH-impact through dynamic, region-contextualized measures.MethodsThis retrospective cohort study assessed GIC patients (20+ years) between 2013 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database for total and subcomponent social vulnerability associations across 15 SDoH-variables encompassing themes of socioeconomic status, minority-language status, household composition, and housing-transportation measured by the Social Vulnerability Index (SVI). These are measured and contextualized from all US counties. Univariate logistic and linear regressions of these vulnerability associations with treatment receipt (chemotherapy, radiation, primary surgery) and survival were performed for the entire cohort and across race/ethnicity strata.ResultsWith increasing overall social vulnerability, 287,248 patients (162,387 [56.5%] male; 185,250 [64.6%] white) demonstrated decreased receipt of chemotherapy (lowest, pancreas-OR, 0.90; 95% CI, 0.88-0.93), radiotherapy (hepatic-OR, 0.87; 95% CI, 0.85-0.89) and surgery (esophagus-OR, 0.90; 95% CI, 0.87-0.92) for 13/14, 10/14, and 8/14 GIC-types, respectively. Survival period decreases upwards of 21.3% (biliary tract: 6.9-5.4 months) were observed across 7/14 GICs. Treatment receipt and survival decreases were exacerbated for non-White patients for 9/14 GICs. Socioeconomic status, minority-language, household composition, and housing-transportation vulnerabilities differentially contributed to these trends.DiscussionSocial vulnerability was associated with worse prognostic and treatment disparities, with certain SDoH-types differentially contributing to these detrimental trends per GIC-type while associations were exacerbated among non-White race/ethnic patients. These real-world contexts present actionable targets for further initiatives to combat GIC disparities.

Project description:The relevance of race and ethnicity to genetics and medicine has long been a matter of debate. An emerging consensus holds that race and ethnicity are social constructs and thus poor proxies for genetic diversity. The goal of this study was to evaluate the relationship between race, ethnicity, and clinically relevant pharmacogenomic variation in cosmopolitan populations. We studied racially and ethnically diverse cohorts of 65,120 participants from the United States All of Us Research Program (All of Us) and 31,396 participants from the United Kingdom Biobank (UKB). Genome-wide patterns of pharmacogenomic variation-6311 drug response-associated variants for All of Us and 5966 variants for UKB-were analyzed with machine learning classifiers to predict participants' self-identified race and ethnicity. Pharmacogenomic variation predicts race/ethnicity with averages of 92.1% accuracy for All of Us and 94.3% accuracy for UKB. Group-specific prediction accuracies range from 99.0% for the White group in UKB to 92.9% for the Hispanic group in All of Us. Prediction accuracies are substantially lower for individuals who identified with more than one group in All of Us (16.7%) or as Mixed in UKB (70.7%). There are numerous individual pharmacogenomic variants with large allele frequency differences between race/ethnicity groups in both cohorts. Frequency differences for toxicity-associated variants predict hundreds of adverse drug reactions per 1000 treated participants for minority groups in All of Us. Our results indicate that race and ethnicity can be used to stratify pharmacogenomic risk in the US and UK populations and should not be discounted when making treatment decisions. We resolve the contradiction between the results reported here and the orthodoxy of race and ethnicity as non-genetic, social constructs by emphasizing the distinction between global and local patterns of human genetic diversity, and we stress the current and future limitations of race and ethnicity as proxies for pharmacogenomic variation.

Dataset Information

Genetic associations with metabolic syndrome and its quantitative traits by race/ethnicity in the United States.

Publications

Genetic associations with metabolic syndrome and its quantitative traits by race/ethnicity in the United States.

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