Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 189, Issue 5, Pages 445-460Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwz251
Keywords
additive interaction; family history; genetic risk score; lifestyle; multiplicative interaction; type 2 diabetes
Categories
Funding
- National Institutes of Health [UM1 CA167552, R01 HL35464, UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, R01 HL088521, HL60712, P30 DK46200, DK091718, HL071981, HL073168, CA87969, CA49449, CA055075, HL34594, HL088521, U01HG004399, DK080140]
- Amgen
- [5P30DK46200]
- [U54CA155626]
- [DK58845]
- [U01HG004728-02]
- [EY015473]
- [DK70756]
- [DK46200]
- [HL043851]
- [HL69757]
- [CA047988]
Ask authors/readers for more resources
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.
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