Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes. Issue 5 (24th October 2019)

• Record Type: Journal Article
• Authors: Ding, Ming; Ahmad, Shafqat; Qi, Lu; Hu, Yang; Bhupathiraju, Shilpa N; Guasch-Ferré, Marta; Jensen, Majken K; Chavarro, Jorge E; Ridker, Paul M; Willett, Walter C; Chasman, Daniel I; Hu, Frank B; Kraft, Peter
• Is Part Of: American journal of epidemiology. Volume 189:Issue 5(2020)
• Page Start: 445
• Page End: 460
• Publication Date: 2019-10-24
• Subjects: additive interaction -- family history -- genetic risk score -- lifestyle -- multiplicative interaction -- type 2 diabetes; Epidemiology -- Periodicals; Public health -- Periodicals; 614.4
• DOI: 10.1093/aje/kwz251
• Languages: English
• ISSNs: 0002-9262

Abstract

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.