Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts release_emhzijnrrngqpm4ydml6odtoee

Abstract

<jats:sec id="sec001"> <jats:title>Background</jats:title> Both 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. </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and findings</jats:title> We 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; <jats:italic>P</jats:italic> &lt; 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; <jats:italic>P</jats:italic> &lt; 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 (<jats:italic>P</jats:italic><jats:sub>interaction</jats:sub> = 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 (<jats:italic>P</jats:italic><jats:sub>interaction</jats:sub> = 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. </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> These 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. </jats:sec>
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