title: Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
abstract: While genome-wide association studies (GWAS) and candidate gene approaches have identified many genetic variants that contribute to disease risk as main effects, the impact of genotype by environment (GxE) interactions remains rather under-surveyed. To explore the importance of GxE interactions for diabetes-related traits, a tool for Genome-wide Complex Trait Analysis (GCTA) was used to examine GxE variance contribution of 15 macronutrients and lifestyle to the total phenotypic variance of diabetes-related traits at the genome-wide level in a European American population. GCTA identified two key environmental factors making significant contributions to the GxE variance for diabetes-related traits: carbohydrate for fasting insulin (25.1% of total variance, P-nominal = 0.032) and homeostasis model assessment of insulin resistance (HOMA-IR) (24.2% of total variance, P-nominal = 0.035), n-6 polyunsaturated fatty acid (PUFA) for HOMA-β-cell-function (39.0% of total variance, P-nominal = 0.005). To demonstrate and support the results from GCTA, a GxE GWAS was conducted with each of the significant dietary factors and a control E factor (dietary protein), which contributed a non-significant GxE variance. We observed that GxE GWAS for the environmental factor contributing a significant GxE variance yielded more significant SNPs than the control factor. For each trait, we selected all significant SNPs produced from GxE GWAS, and conducted anew the GCTA to estimate the variance they contributed. We noted the variance contributed by these SNPs is higher than that of the control. In conclusion, we utilized a novel method that demonstrates the importance of genome-wide GxE interactions in explaining the variance of diabetes-related traits.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China ; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Zheng
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage; D005260:Female; D059647:Gene-Environment Interaction; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D014481:United States; D044465:White People
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D043371:Fatty Acids, Omega-6