Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes
Year: 2019
Type: article
Study design: Observational Study
Abstract: We examined interactions between lifestyle factors and genetic risk of type 2 diabetes (T2D-GR), captured by genetic risk score (GRS) and family history (FH). Our initial study cohort included 20,524 European-ancestry participants, of whom 1,897 developed incident T2D, in the Nurses' Health Study (1984-2016), Nurses' Health Study II (1989-2016), and Health Professionals Follow-up Study (1986-2016). The analyses were replicated in 19,183 European-ancestry controls and 2,850 incident T2D cases in the Women's Genome Health Study (1992-2016). We defined 2 categories of T2D-GR: high GRS (upper one-third) with FH and low GRS or without FH. Compared with participants with the healthiest lifestyle and low T2D-GR, the relative risk of T2D for participants with the healthiest lifestyle and high T2D-GR was 2.24 (95% confidence interval (CI): 1.76, 2.86); for participants with the least healthy lifestyle and low T2D-GR, it was 4.05 (95% CI: 3.56, 4.62); and for participants with the least healthy lifestyle and high T2D-GR, it was 8.72 (95% CI: 7.46, 10.19). We found a significant departure from an additive risk difference model in both the initial and replication cohorts, suggesting that adherence to a healthy lifestyle could lead to greater absolute risk reduction among those with high T2D-GR. The public health implication is that a healthy lifestyle is important for diabetes prevention, especially for individuals with high GRS and FH of T2D.
Source: American Journal of Epidemiology
DOI: 10.1093/aje/kwz251
Institution: Harvard University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Dietary Patterns and Risk of Cardiovascular Disease, Obesity Genes, Energy Regulation in Response to Weight-Loss Diets, G1717613936, Genetic Markers of CHD in Type 2 Diabetes, G229684361, Biochemical Markers in the nurses' Health Study Cohort, Genes and Environment Initiatives in Type 2 Diabetes, Gene-Environment Interactions in Glaucoma, Biochemical and Genetic Markers of Type 2 Diabetes Risk, Pharmacogenomics and Risk of Cardiovascular Disease, Dietary Etiologies of Heart Disease, Boston Nutrition Obesity Research Center, Dietary and Hormonal Determinants of Cancer in Women, Genes and Environment Initiative in Glaucoma, Genetics of Coronary Artery Disease in Type 2 Diabetes, G459566519, Pharmacogenomics and Risk of Cardiovascular Disease, The Pathobiology of Nephrolithiasis, Harvard Transdisciplinary Research in Energetics and Cancer Center, Epidemiology of Precursors to Type 2 Diabetes, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, Prospective Studies of Diet and Cancer in Men and Women, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study, Biochemical Markers in the Nurses? Health Study Cohort, Women's Health Study: Continued Follow-up, Cancer Epidemiology Cohort in Male Health Professionals, G9000003116, G9000019617, G9000028950, G9000029955, G9000043482, G9000058182, G9000158339, G9000190097, G9000207591, G9000282657, G9000332794, RISK FACTORS FOR CVD IN WOMEN, Risk Factors for Ischemic Stroke in Women
OpenAlex ID: W2979970094