Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits.
Journal
Nature human behaviour
ISSN: 2397-3374
Titre abrégé: Nat Hum Behav
Pays: England
ID NLM: 101697750
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
04
06
2018
accepted:
22
02
2019
pubmed:
10
4
2019
medline:
23
11
2019
entrez:
10
4
2019
Statut:
ppublish
Résumé
Genetic correlations estimated from genome-wide association studies (GWASs) reveal pervasive pleiotropy across a wide variety of phenotypes. We introduce genomic structural equation modelling (genomic SEM): a multivariate method for analysing the joint genetic architecture of complex traits. Genomic SEM synthesizes genetic correlations and single-nucleotide polymorphism heritabilities inferred from GWAS summary statistics of individual traits from samples with varying and unknown degrees of overlap. Genomic SEM can be used to model multivariate genetic associations among phenotypes, identify variants with effects on general dimensions of cross-trait liability, calculate more predictive polygenic scores and identify loci that cause divergence between traits. We demonstrate several applications of genomic SEM, including a joint analysis of summary statistics from five psychiatric traits. We identify 27 independent single-nucleotide polymorphisms not previously identified in the contributing univariate GWASs. Polygenic scores from genomic SEM consistently outperform those from univariate GWASs. Genomic SEM is flexible and open ended, and allows for continuous innovation in multivariate genetic analysis.
Identifiants
pubmed: 30962613
doi: 10.1038/s41562-019-0566-x
pii: 10.1038/s41562-019-0566-x
pmc: PMC6520146
mid: NIHMS1522525
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
513-525Subventions
Organisme : NIA NIH HHS
ID : R01 AG054628
Pays : United States
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : P2C HD042849
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD083613
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F019394/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
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