Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts

Author summary Why was this study done? Both genetic and lifestyle factors contribute to individual-level risk of type 2 diabetes.While previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes regardless of genetic risk, the partial characterization of genetic risk and the predominant assessment of interactions on the multiplicative scale might have prevented previous studies from identifying genetic profiles interacting with dietary exposures.Therefore, understanding how genetic risk and diet quality contribute to the development of type 2 diabetes is important to support evidence-based preventive interventions. What did the researchers do and find? In 3 cohort studies involving 35,759 men and women in the US, we used novel polygenic scores for type 2 diabetes to systematically evaluate the presence of additive and multiplicative interactions between genetic risk and diet quality on the development of type 2 diabetes.We found that both low diet quality and increased overall or pathway-specific genetic risk were independently associated with higher risk of type 2 diabetes.We documented that within any genetic risk category, high diet quality, as compared to low diet quality, was associated with a nearly 30% lower risk of type 2 diabetes.Further, we showed that the risk of type 2 diabetes attributed to the combination of increased genetic risk and low diet quality was similar to the sum of the risks associated with each factor alone. What do these findings mean? Results from this study suggest that consuming a healthier diet is associated with a lower risk of type 2 diabetes regardless of genetic risk.Our results underscore the value of genetic risk assessment to identify individuals at increased disease risk and their potential for risk stratification and surveillance.Such knowledge can serve to inform and design future strategies to advance the prevention of type 2 diabetes. BackgroundBoth genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findingsWe analyzed data from 35,759 men and women in the United States participating in the Nurses' Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (P-interaction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (P-interaction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. ConclusionsThese data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.