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Gene-carbohydrate and gene-fiber interactions and type 2 diabetes in diverse populations from the National Health and Nutrition Examination Surveys (NHANES) as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study

Raquel Villegas1*, Robert J Goodloe3, Bob E McClellan3, Jonathan Boston3 and Dana C Crawford23

Author Affiliations

1 Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, TN 37203-1738, USA

2 Molecular Physiology and Biophysics, 1211 Medical Center Drive, Nashville, TN 37232, USA

3 Center for Human Genetics Research, 519 Light Hall Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232-0700, USA

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BMC Genetics 2014, 15:69  doi:10.1186/1471-2156-15-69

Published: 14 June 2014



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.


We 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.


Our results suggest that dietary carbohydrates and fiber may modify T2D-associated variants, highlighting the importance of dietary nutrients in predicting T2D risk.

Type 2 diabetes; Carbohydrate; Fiber; Gene