Phenome-wide Burden of Copy-Number Variation in the UK Biobank.

TitlePhenome-wide Burden of Copy-Number Variation in the UK Biobank.
Publication TypeJournal Article
Year of Publication2019
AuthorsAguirre, M, Rivas, MA, Priest, J
JournalAm J Hum Genet
Date Published2019 Aug 01

Copy-number variations (CNVs) 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 potentially pathogenic and previously uncharacterized CNV loci across more than 3,000 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, previously uncharacterized variation at 9p23, and several genic associations 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 dosage-mediated genic associations across the medical phenome.

Alternate JournalAm. J. Hum. Genet.
PubMed ID31353025
PubMed Central IDPMC6699064
Grant ListR00 HL130523 / HL / NHLBI NIH HHS / United States
R01 HG010140 / HG / NHGRI NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States