Comprehensive genetic study of the insulin resistance marker TG:HDL-C in the UK Biobank

胰岛素抵抗 生物 全基因组关联研究 生命银行 单核苷酸多态性 2型糖尿病 遗传学 内科学 候选基因 代谢综合征 内分泌学 生物信息学 糖尿病 基因型 基因 医学
作者
Antonino Oliveri,Ryan Rebernick,Annapurna Kuppa,Asmita Pant,Yanhua Chen,Xiaomeng Du,Kelly C. Cushing,Hannah N. Bell,Chinmay Raut,Ponnandy Prabhu,Vincent Chen,Brian Halligan,Elizabeth K. Speliotes
出处
期刊:Nature Genetics [Nature Portfolio]
卷期号:56 (2): 212-221 被引量:47
标识
DOI:10.1038/s41588-023-01625-2
摘要

Insulin resistance (IR) is a well-established risk factor for metabolic disease. The ratio of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) is a surrogate marker of IR. We conducted a genome-wide association study of the TG:HDL-C ratio in 402,398 Europeans within the UK Biobank. We identified 369 independent SNPs, of which 114 had a false discovery rate-adjusted P value < 0.05 in other genome-wide studies of IR making them high-confidence IR-associated loci. Seventy-two of these 114 loci have not been previously associated with IR. These 114 loci cluster into five groups upon phenome-wide analysis and are enriched for candidate genes important in insulin signaling, adipocyte physiology and protein metabolism. We created a polygenic-risk score from the high-confidence IR-associated loci using 51,550 European individuals in the Michigan Genomics Initiative. We identified associations with diabetes, hyperglyceridemia, hypertension, nonalcoholic fatty liver disease and ischemic heart disease. Collectively, this study provides insight into the genes, pathways, tissues and subtypes critical in IR. Genome-wide association analysis of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio within the UK Biobank identifies candidate insulin resistance-associated loci linked to metabolic pathways and insulin biology. A polygenic risk score derived from these results shows an association with multiple cardiometabolic traits.
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