Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes

Ming Ding, Shafqat Ahmad, Lu Qi, Yang Hu, Shilpa N Bhupathiraju, Marta Guasch-Ferré, Majken K Jensen, Jorge E Chavarro, Paul M Ridker, Walter C Willett, Daniel I Chasman, Frank B Hu, Peter Kraft

PMID: 31647510
DOI: 10.1093/aje/kwz251

Erratum in

RE: "ADDITIVE AND MULTIPLICATIVE INTERACTIONS BETWEEN GENETIC RISK SCORE AND FAMILY HISTORY AND LIFESTYLE IN RELATION TO RISK OF TYPE 2 DIABETES".
Am J Epidemiol. 2020 May 5;189(5):483. doi: 10.1093/aje/kwaa063.PMID: 32412063 No abstract available.

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.

Keywords: additive interaction; family history; genetic risk score; lifestyle; multiplicative interaction; type 2 diabetes.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.