title: Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes.
abstract: Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2D, and the interaction of baseline TG with TG genetic risk on incident T2D in 13,247 European-Americans (EA) and 3,238 African-Americans (AA) from three prospective cohort studies. A TG genetic risk score (GRS) was calculated based on 31 validated single nucleotide polymorphisms (SNPs). We considered several baseline covariates, including body- mass index (BMI) and lipid traits. Among EA and AA, we find, as expected, that baseline levels of TG are strongly positively associated with incident T2D (p<2 x 10-(10)). However, the TG GRS is negatively associated with T2D (p=0.013), upon adjusting for only race, in the full dataset. Upon additionally adjusting for age, sex, BMI, high-density lipoprotein cholesterol and TG, the TG GRS is significantly and negatively associated with T2D incidence (p=7.0 x 10(-8)), with similar trends among both EA and AA. No single SNP appears to be driving this association. We also find a significant statistical interaction of the TG GRS with TG (pi(nteraction) = 3.3 x 10-(4)), whereby the association of TG with incident T2D is strongest among those with low genetic risk for TG. Further research is needed to understand the likely pleiotropic mechanisms underlying these findings, and to clarify the causal relationship between T2D and TG.
authors.affiliation: Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.affiliation: Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Akshay
authors.initials: A
authors.lastname: Chougule
authors.affiliation: Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Arora
authors.affiliation: USDA / ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.affiliation: Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Chiu-Hsieh
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood* / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D014280:Triglycerides