Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.
African ancestry
fine-mapping
genome-wide
height
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 04 2021
01 04 2021
Historique:
received:
05
06
2020
accepted:
09
02
2021
pubmed:
14
3
2021
medline:
8
5
2021
entrez:
13
3
2021
Statut:
ppublish
Résumé
Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
Identifiants
pubmed: 33713608
pii: S0002-9297(21)00053-7
doi: 10.1016/j.ajhg.2021.02.011
pmc: PMC8059339
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
564-582Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL143885
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008692
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA229995
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK075787
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129982
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK110919
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD100406
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD058886
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148469
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149683
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135405
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL154284
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD057194
Pays : United States
Informations de copyright
Copyright © 2021 American Society of Human Genetics. All rights reserved.
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