Phenome-wide Burden of Copy-Number Variation in the UK Biobank.
Autistic Disorder
/ genetics
Biological Specimen Banks
Case-Control Studies
Chromosome Deletion
Chromosome Disorders
/ genetics
Chromosomes, Human, Pair 16
/ genetics
Chromosomes, Human, Pair 9
/ genetics
Coronary Artery Disease
/ genetics
DNA Copy Number Variations
DiGeorge Syndrome
/ genetics
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Intellectual Disability
/ genetics
Male
Phenomics
Phenotype
Polymorphism, Single Nucleotide
United Kingdom
UK Biobank
association testing
copy number variation
genetics
genomics
microdeletion/microduplication syndrome
population database
selection bias
structural variation
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
06
03
2019
accepted:
28
06
2019
pubmed:
30
7
2019
medline:
17
3
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31353025
pii: S0002-9297(19)30264-2
doi: 10.1016/j.ajhg.2019.07.001
pmc: PMC6699064
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
373-383Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG010140
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Informations de copyright
Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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