Identifying cross-disease components of genetic risk across hospital data in the UK Biobank.
Adult
Aged
Biological Specimen Banks
Female
Gene-Environment Interaction
Genetic Diseases, Inborn
/ genetics
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Prospective Studies
Quantitative Trait, Heritable
Risk Factors
United Kingdom
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
25
03
2019
accepted:
18
11
2019
pubmed:
25
12
2019
medline:
9
4
2020
entrez:
25
12
2019
Statut:
ppublish
Résumé
Genetic risk factors frequently affect multiple common human diseases, providing insight into shared pathophysiological pathways and opportunities for therapeutic development. However, systematic identification of genetic profiles of disease risk is limited by the availability of both comprehensive clinical data on population-scale cohorts and the lack of suitable statistical methodology that can handle the scale of and differential power inherent in multi-phenotype data. Here, we develop a disease-agnostic approach to cluster the genetic risk profiles for 3,025 genome-wide independent loci across 19,155 disease classification codes from 320,644 participants in the UK Biobank, representing a large and heterogeneous population. We identify 339 distinct disease association profiles and use multiple approaches to link clusters to the underlying biological pathways. We show how clusters can decompose the variance and covariance in risk for disease, thereby identifying underlying biological processes and their impact. We demonstrate the use of clusters in defining disease relationships and their potential in informing therapeutic strategies.
Identifiants
pubmed: 31873298
doi: 10.1038/s41588-019-0550-4
pii: 10.1038/s41588-019-0550-4
pmc: PMC6974401
mid: EMS84971
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126-134Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204290/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/3
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100956
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 090532
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/3
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100308
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204290
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom
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