2026-04-17T01:52:08Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/417462025-12-18T01:14:41Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Emdin, Connor A. author Elosua Llanos, Roberto author Kathiresan, Sekar author 2019-06-13T06:24:16Z 2019-06-13T06:24:16Z 2018 Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency < 5%) pLOF variant-phenotype associations. pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, in the gene IL33 against asthma and allergic disease, and in the gene IFIH1 against hypothyroidism. In the gene PDE3B, pLOF variants associate with elevated height, improved body fat distribution and protection from coronary artery disease. Our findings prioritize genes for which pharmacologic mimics of pLOF variants may lower risk for disease. Diabetis Fenotip Metabolisme Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease