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To determine whether unhealthy lifestyle behaviors were associated with similar increases in the risk of incident T2D among individuals with low, intermediate, and high genetic risk, we performed a genetic risk score (GRS) by lifestyle interaction analysis within 460,133 individuals from the UK Biobank. Multi-ancestry GRS were calculated by summing the effects of 1,286 T2D-associated variants (number of risk alleles multiplied by the reported effect size); low, intermediate, and high GRS were defined by tertiles of GRS. We used baseline self-reported data on smoking, BMI, physical activity, and diet to categorize participants as having an ideal, intermediate, or poor level of lifestyle factors. Cox proportional hazards regression models were used to generate adjusted hazards ratios (HR) and associated 95% confidence intervals (95% CI). During follow-up (median 8.9 years), 21,569 (4.7%) participants developed T2D. GRS (P2e-16) and lifestyle classification (P2e-16) were independently associated with increased risk for T2D. Compared with “ideal” lifestyle, “poor” lifestyle was associated with substantially increased risk in all genetic risk strata, with HR ranging from 7.5 to 29.5 (Figure 1). Overall, high genetic risk and poor lifestyle were the strongest risk factors for incident T2D. Individuals at all levels of genetic risk greatly mitigate their risk through their behavioral lifestyle. Disclosure C.N. Spracklen: None. C. Zhao: None. E. Bertone-Johnson: None. N. Cai: None. L. Huang: None. M. Janiczek: None. C. Lee: None. C. Ma: None. A. Paluch: None. S. sturgeon: None. N. VanKim: None. Funding American Diabetes Association (11-22-JDFPM-06)
Spracklen et al. (Fri,) studied this question.
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