RT Journal Article
SR Electronic
T1 Phenome-wide burden of copy number variation in UK Biobank
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 545996
DO 10.1101/545996
A1 Matthew Aguirre
A1 Manuel Rivas
A1 James Priest
YR 2019
UL http://biorxiv.org/content/early/2019/02/10/545996.abstract
AB Copy number variations (CNV) represent a significant proportion of the genetic differences between individuals and many CNVs associate causally with syndromic disease and clinical outcomes. Here, we characterize the landscape of copy number variation and their phenome-wide effects in a sample of 472,228 array-genotyped individuals from the UK Biobank. In addition to population-level selection effects against genic loci conferring high-mortality, we describe genetic burden from syndromic and previously uncharacterized CNV loci across nearly 2,000 quantitative and dichotomous traits, with separate analyses for common and rare classes of variation. Specifically, we highlight the effects of CNVs at two well-known syndromic loci 16p11.2 and 22q11.2, as well as novel associations at 9p23, in the context of acute coronary artery disease and high body mass index. Our data constitute a deeply contextualized portrait of population-wide burden of copy number variation, as well as a series of known and novel dosage-mediated genic associations across the medical phenome.