Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes
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Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes. / 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.
In: American Journal of Epidemiology, Vol. 189, No. 5, 2020, p. 445-460.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes
AU - Ding, Ming
AU - Ahmad, Shafqat
AU - Qi, Lu
AU - Hu, Yang
AU - Bhupathiraju, Shilpa N.
AU - Guasch-Ferré, Marta
AU - Jensen, Majken K.
AU - Chavarro, Jorge E.
AU - Ridker, Paul M.
AU - Willett, Walter C.
AU - Chasman, Daniel I.
AU - Hu, Frank B.
AU - Kraft, Peter
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - additive interaction
KW - family history
KW - genetic risk score
KW - lifestyle
KW - multiplicative interaction
KW - type 2 diabetes
U2 - 10.1093/aje/kwz251
DO - 10.1093/aje/kwz251
M3 - Journal article
C2 - 31647510
AN - SCOPUS:85086792732
VL - 189
SP - 445
EP - 460
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
SN - 0002-9262
IS - 5
ER -
ID: 244625254