Effects of pathogenic CNVs on physical traits in participants of the UK Biobank

Abstract Background Copy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them have been associated with changes in weight, height, and other physical traits. As most studies have been performed on children and young people, these effects of CNVs in middle-aged and older people are not well established. The UK Biobank recruited half a million adults who provided a variety of physical measurements. We called all CNVs from the Affymetrix microarrays and selected a set of 54 CNVs implicated as pathogenic (including their reciprocal deletions/duplications) and that were found in five or more persons. Linear regression analysis was used to establish their association with 16 physical traits relevant to human health. Results 396,725 participants of white British or Irish descent (excluding first-degree relatives) passed our quality control filters. Out of the 864 CNV/trait associations, 214 were significant at a false discovery rate of 0.1, most of them novel. Many of these traits increase risk for adverse health outcomes: e.g. increases in weight, waist-to-hip ratio, pulse rate and body fat composition. Deletions at 16p11.2, 16p12.1, NRXN1 and duplications at 16p13.11 and 22q11.2 produced the highest numbers of significant associations. Five CNVs produced average changes of over one standard deviation for the 16 traits, compared to controls: deletions at 16p11.2 and 22q11.2, and duplications at 3q29, the Williams-Beuren and Potocki-Lupski regions. CNVs at 1q21.1, 2q13, 16p11.2 and 16p11.2 distal, 16p12.1, 17p12 and 17q12 demonstrated one or more mirror image effects of deletions versus duplications. Conclusions Carriers of many CNVs should be monitored for physical traits that increase morbidity and mortality. Genes within these CNVs can give insights into biological processes and therapeutic interventions