RT Journal Article
SR Electronic
T1 Effects of pathogenic CNVs on physical traits in participants of the UK Biobank
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 355297
DO 10.1101/355297
A1 David Owen
A1 Mathew Bracher-Smith
A1 Kimberley Kendall
A1 Elliott Rees
A1 Mark Einon
A1 Valentina Escott-Price
A1 Michael J Owen
A1 Michael C O’Donovan
A1 George Kirov
YR 2018
UL http://biorxiv.org/content/early/2018/06/25/355297.abstract
AB 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 adulthood are not well established.Methods 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 present 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. There were 214 CNV/trait associations significant at a false discovery rate of 0.1, most of them novel. These traits are associated with adverse health outcomes: e.g. increased 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. CNVs at 1q21.1, 2q13, 16p11.2, 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.