Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements.
Asian People
/ genetics
Base Sequence
Computational Biology
/ methods
Enhancer Elements, Genetic
/ genetics
Gene Expression Regulation
/ genetics
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
Humans
Models, Genetic
Molecular Sequence Annotation
Multifactorial Inheritance
/ genetics
Polymorphism, Single Nucleotide
/ genetics
White People
/ genetics
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
21
02
2020
accepted:
19
10
2020
pubmed:
2
12
2020
medline:
26
1
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
Poor trans-ancestry portability of polygenic risk scores is a consequence of Eurocentric genetic studies and limited knowledge of shared causal variants. Leveraging regulatory annotations may improve portability by prioritizing functional over tagging variants. We constructed a resource of 707 cell-type-specific IMPACT regulatory annotations by aggregating 5,345 epigenetic datasets to predict binding patterns of 142 transcription factors across 245 cell types. We then partitioned the common SNP heritability of 111 genome-wide association study summary statistics of European (average n ≈ 189,000) and East Asian (average n ≈ 157,000) origin. IMPACT annotations captured consistent SNP heritability between populations, suggesting prioritization of shared functional variants. Variant prioritization using IMPACT resulted in increased trans-ancestry portability of polygenic risk scores from Europeans to East Asians across all 21 phenotypes analyzed (49.9% mean relative increase in R
Identifiants
pubmed: 33257898
doi: 10.1038/s41588-020-00740-8
pii: 10.1038/s41588-020-00740-8
pmc: PMC8049522
mid: NIHMS1689007
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1346-1354Subventions
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR063759
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009088
Pays : United States
Organisme : Medical Research Council
ID : MR/R013926/1
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U01 HG009379
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067677
Pays : United States
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