Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
PLoS Med. 2022 Apr 26;19(4):e1003972. doi: 10.1371/journal.pmed.1003972. eCollection 2022 Apr.
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.
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; 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 (Pinteraction = 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 (Pinteraction = 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.
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.
遗传和生活方式因素都会增加 2 型糖尿病的风险，但这两种因素协同作用的程度尚不清楚。本研究旨在探讨遗传风险和饮食质量与 2 型糖尿病发病的联合关联。
我们分析了美国参加护士健康研究（NHS）I（1986 年至 2016 年）和 II（1991 年至 2017 年）以及健康专业人员随访研究（HPFS；1986 年至 2016 年）的 35759 名男性和女性的数据，这些人在基线时没有糖尿病、心血管疾病或癌症，且有可用的遗传数据。遗传风险通过使用一种捕获整体遗传风险的综合多基因评分和表示不同病理生理机制的途径特异性多基因评分来描述。饮食质量使用替代健康饮食指数（AHEI）进行评估。Cox 模型用于调整潜在混杂因素后计算 2 型糖尿病的风险比（HR）。在超过 902386 人年的随访中，有 4433 名参与者被诊断为 2 型糖尿病。全球多基因评分每增加一个标准差（SD），2 型糖尿病的相对风险增加 1.29（95%置信区间[CI] 1.25，1.32；P<0.001），AHEI 每降低 10 个单位，风险增加 1.13（1.09，1.17；P<0.001）。无论遗传风险如何，与饮食质量高相比，饮食质量低与 2 型糖尿病风险增加约 30%相关（P 交互作用=0.69）。低饮食质量和遗传风险增加的联合关联与每个因素单独相关的风险总和相似（P 交互作用=0.30）。本研究的局限性包括饮食信息的自我报告以及由于纳入具有可用遗传数据的受过高等教育的参与者而可能导致的偏倚。
这些数据为遗传风险和饮食质量与 2 型糖尿病发病的独立关联提供了证据，并表明健康饮食与遗传风险水平无关，与较低的糖尿病风险相关。
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