Abstract
BackgroundBoth environmental and genetic factors impact type 2 diabetes (T2D). To identify such modifiers, we genotyped 15 T2D-associated variants from genome-wide association studies (GWAS) in 6,414 non-Hispanic whites, 3,073 non-Hispanic blacks, and 3,633 Mexican American participants from the National Health and Nutrition Examination Surveys (NHANES) and evaluated interactions between these variants and carbohydrate intake and fiber intake.ResultsWe calculated a genetic risk score (GRS) with the 15 SNPs. The odds ratio for T2D with each GRS point was 1.10 (95% CI: 1.05-1.14) for non-Hispanic whites, 1.07 (95% CI: 1.02-1.13) for non-Hispanic blacks, and 1.11 (95% CI: 1.06-1.17) for Mexican Americans. We identified two gene-carbohydrate interactions (P < 0.05) in non-Hispanic whites (with CDKAL1 rs471253 and FTO rs8050136), two in non-Hispanic blacks (with IGFBP2 rs4402960 and THADA rs7578597), and two in Mexican Americans (with NOTCH2 rs1092398 and TSPAN8-LGRS rs7961581). We found three gene-fiber interactions in non-Hispanic whites (with ADAMT59 rs4607103, CDKN2A/2B rs1801282, and FTO rs8050136), two in non-Hispanic blacks (with ADAMT59 rs4607103 and THADA rs7578597), and two in Mexican Americans (with THADA rs7578597 and TSPAN8-LGRS rs796158) at the P < 0.05 level. Interactions between the GRS and nutrients failed to reach significance in all the racial/ethnic groups.ConclusionOur results suggest that dietary carbohydrates and fiber may modify T2D-associated variants, highlighting the importance of dietary nutrients in predicting T2D risk.
Highlights
Both environmental and genetic factors impact type 2 diabetes (T2D)
We investigated associations between T2D and genetic variants discovered by genome-wide association studies (GWAS) in three racial/ethnic groups and modifications of these associations by carbohydrate and fiber intake
We evaluated the combined effect of genetic variants by calculating a genetic risk score (GRS) and examined possible interactions of the GRS with carbohydrate intake and fiber across the three racial/ethnic groups
Summary
Both environmental and genetic factors impact type 2 diabetes (T2D). To identify such modifiers, we genotyped 15 T2D-associated variants from genome-wide association studies (GWAS) in 6,414 non-Hispanic whites, 3,073 non-Hispanic blacks, and 3,633 Mexican American participants from the National Health and Nutrition Examination Surveys (NHANES) and evaluated interactions between these variants and carbohydrate intake and fiber intake. For the past few years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including type 2 diabetes (T2D). Insulin is secreted in response to elevated blood glucose concentration; dietary carbohydrates, which influence glucose concentration and insulin demands [4], may modify associations between GWAS variants and T2D. Fiber has been associated with lower risk of T2D [5,6]
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