Questionnaire-Based Polyexposure Assessment Outperforms Polygenic Scores for Classification of Type 2 Diabetes in a Multiancestry Cohort.
Questionnaire-Based Polyexposure Assessment Outperforms Polygenic Scores for Classification of Type 2 Diabetes in a Multiancestry Cohort.
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环境暴露可能比多基因评分（PGS）对2型糖尿病有更大的预测能力。然而，研究环境风险因素的研究仅包括具有欧洲血统的个体，限制了结果的适用性。我们在多祖先个性化环境和基因研究中进行了一项全人群关联研究，以评估环境因素对2型糖尿病的影响。使用logistic回归进行单次暴露分析，我们确定了与2型糖尿病相关的暴露，调整了年龄，BMI，家庭收入以及自我报告的性别和种族。为了比较累积的遗传和环境影响，我们计算了总体临床评分（OCS）作为BMI和前驱糖尿病，高血压和高胆固醇状态的加权和，以及多重暴露评分（PXS）作为13个环境变量的加权和。使用英国生物银行的数据，我们开发了一个多祖先PGS，并为参与者计算了它。我们发现了76种与2型糖尿病的显著关联，包括石棉和煤尘暴露的新关联。OCS、PXS和PGS与2型糖尿病显著相关。PXS有中等的权力，以确定协会，更大的效果大小和更大的权力和重新分类的改善比PGS。对于所有分数，结果因种族而异。我们在多祖先队列中的发现阐明了2型糖尿病的几率如何归因于临床，遗传和环境因素，并强调了在疾病风险相关研究中需要麻烦的数据。基于种族的预测得分差异突出了在不同人群中进行遗传和全基因组研究的必要性。
Environmental exposures may have greater predictive power for type 2 diabetes than polygenic scores (PGS). Studies examining environmental risk factors, however, have included only individuals with European ancestry, limiting the applicability of results. We conducted an exposome-wide association study in the multiancestry Personalized Environment and Genes Study to assess the effects of environmental factors on type 2 diabetes. Using logistic regression for single-exposure analysis, we identified exposures associated with type 2 diabetes, adjusting for age, BMI, household income, and self-reported sex and race. To compare cumulative genetic and environmental effects, we computed an overall clinical score (OCS) as a weighted sum of BMI and prediabetes, hypertension, and high cholesterol status and a polyexposure score (PXS) as a weighted sum of 13 environmental variables. Using UK Biobank data, we developed a multiancestry PGS and calculated it for participants. We found 76 significant associations with type 2 diabetes, including novel associations of asbestos and coal dust exposure. OCS, PXS, and PGS were significantly associated with type 2 diabetes. PXS had moderate power to determine associations, with larger effect size and greater power and reclassification improvement than PGS. For all scores, the results differed by race. Our findings in a multiancestry cohort elucidate how type 2 diabetes odds can be attributed to clinical, genetic, and environmental factors and emphasize the need for exposome data in disease-risk association studies. Race-based differences in predictive scores highlight the need for genetic and exposome-wide studies in diverse populations.