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The American Journal of Human Genetics
Article
License: Elsevier Non-Commercial
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The American Journal of Human Genetics
Article . 2021 . Peer-reviewed
License: Elsevier Non-Commercial
Data sources: Crossref
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Article . 2021
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Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Authors: Zhao, Jing Hua; Mosley, Thomas H.; Atwood, Larry; Falusi, Adeyinka G.; Conti, David V.; Schurmann, Claudia; Schreiner, Pamela J.; +193 Authors

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Abstract

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.

Countries
United States, United Kingdom
Keywords

Male, Medical Sciences, 610, Black People, Medical and Health Sciences, Polymorphism, Single Nucleotide, genome-wide, Medical Specialties, Medicine and Health Sciences, Genetics, Humans, Polymorphism, Genetics & Heredity, Human Genome, Single Nucleotide, Biological Sciences, Body Height, Black or African American, Europe, fine-mapping, African ancestry, Africa, Female, Genetic Phenomena, height, Genome-Wide Association Study

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
29
Top 10%
Top 10%
Top 10%
Green
hybrid