Phenome-wide burden of copy number variation in UK Biobank [article]

Matthew Aguirre, Manuel Rivas, James Priest
2019 bioRxiv   pre-print
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
more » ... iously 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.
doi:10.1101/545996 fatcat:necuqsvyffehbhypoyhf4a323a