Polyexposure score for T2D Genome-Wide Association Summary Statistics

While genotypes, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. In the following, we identify genetic determinants of a “polyexposure risk score” (PXS), a risk score that summarizes environmental and behavioral risk factors that predict longitudinal T2D incidence consisting of 25 associated individual-level behaviors in the UK Biobank. PXS-T2D had a non-zero heritability (h² = 0.18), and we find extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [r_g] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (r_g = 0.51). Genes associated with PXS-T2D were enriched for expression in the brain. Leveraging biobank scale data with genetic information can inform how exposure and behavior impact T2D across axes of diabetes risk. Enclosed are PXS-T2D GWAS summary statistics (both unadjusted and adjusted by body mass index).

尽管在2型糖尿病（type 2 diabetes, T2D）中，基因型、行为模式与环境暴露构成了一张相互关联的复杂网络，但学界对三者间的交互作用仍知之甚少。本研究首先明确了多暴露风险评分（polyexposure risk score, PXS）的遗传决定因素：该风险评分汇总了可预测纵向2型糖尿病发病的环境与行为风险因素，其行为风险因素来自英国生物库（UK Biobank）中的25项关联个体水平行为指标。PXS-T2D具有非零遗传力（h² = 0.18）；研究发现其与已确立的2型糖尿病临床及生物学决定因素存在广泛的共享遗传结构，其中与体重指数（body mass index，遗传相关系数r_g = 0.57）及胰岛素抵抗稳态模型评估（Homeostatic Model Assessment for Insulin Resistance，r_g = 0.51）的遗传相关性最为显著。与PXS-T2D相关的基因在脑组织中呈现表达富集特征。借助兼具遗传信息的生物库规模级数据，可揭示暴露与行为因素如何从糖尿病风险的多个维度影响2型糖尿病的发生发展。本数据集附带PXS-T2D的全基因组关联研究（Genome-Wide Association Study, GWAS）汇总统计数据，包含未校正及经体重指数校正的两类结果。