Genetic Determinants of Clustering of Cardiometabolic Risk Factors in U.K. Biobank.

Objective: The metabolic syndrome (MetS) is a description of a clustering of cardiometabolic risk factors in the same individual. This study searched for genetic loci associated with all five prespecified components of MetS to find a common pathophysiological link for this risk factor clustering. Methods: Using data from 291,107 individuals in the U.K. biobank, a genome-wide association study (GWAS) was performed versus each of the five components of the syndrome as continuous variables (glucose, systolic blood pressure, triglycerides, waist circumference, and high-density lipoprotein-cholesterol). Results: Using false discovery rate <0.05, three loci were related to all five MetS components (rs7575523; nearest gene LINC0112, rs3936511; intron of C5orf67, and rs111970447; intron of GIP). Of those, C5orf67 seems the most interesting candidate for clustering of risk factors, since previous GWASs in other samples have identified this locus as being related to all five risk factors. Also, genetic loci being related to the different combinations of four or three MetS components were presented. Generally, each MetS component combination was related to a unique genetic profile, and the genetic overlap between these combinations was low. Conclusion: A genetic locus was discovered being related to each of the five MetS components, being a candidate for a common pathophysiological link for risk factor clustering. In addition, genetic loci being related to different combinations of four or three MetS components were presented, and the genetic overlap between those combinations of MetS was low.

291,107 British ancestry individuals