Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.

Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci pr...

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Autores principales: Daniel Shriner, Adebowale Adeyemo, Norman P Gerry, Alan Herbert, Guanjie Chen, Ayo Doumatey, Hanxia Huang, Jie Zhou, Michael F Christman, Charles N Rotimi
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/2946079f73ef4dcebe17e2658c806f5e
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spelling oai:doaj.org-article:2946079f73ef4dcebe17e2658c806f5e2021-11-25T06:27:13ZTransferability and fine-mapping of genome-wide associated loci for adult height across human populations.1932-620310.1371/journal.pone.0008398https://doaj.org/article/2946079f73ef4dcebe17e2658c806f5e2009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20027299/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values < or =0.05 under an additive genetic model with directionally consistent effects) to our African American sample. However, when we comprehensively evaluated all HapMap variants in linkage disequilibrium (r(2) > or = 0.3) with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations.Daniel ShrinerAdebowale AdeyemoNorman P GerryAlan HerbertGuanjie ChenAyo DoumateyHanxia HuangJie ZhouMichael F ChristmanCharles N RotimiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8398 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daniel Shriner
Adebowale Adeyemo
Norman P Gerry
Alan Herbert
Guanjie Chen
Ayo Doumatey
Hanxia Huang
Jie Zhou
Michael F Christman
Charles N Rotimi
Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
description Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values < or =0.05 under an additive genetic model with directionally consistent effects) to our African American sample. However, when we comprehensively evaluated all HapMap variants in linkage disequilibrium (r(2) > or = 0.3) with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations.
format article
author Daniel Shriner
Adebowale Adeyemo
Norman P Gerry
Alan Herbert
Guanjie Chen
Ayo Doumatey
Hanxia Huang
Jie Zhou
Michael F Christman
Charles N Rotimi
author_facet Daniel Shriner
Adebowale Adeyemo
Norman P Gerry
Alan Herbert
Guanjie Chen
Ayo Doumatey
Hanxia Huang
Jie Zhou
Michael F Christman
Charles N Rotimi
author_sort Daniel Shriner
title Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
title_short Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
title_full Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
title_fullStr Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
title_full_unstemmed Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
title_sort transferability and fine-mapping of genome-wide associated loci for adult height across human populations.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/2946079f73ef4dcebe17e2658c806f5e
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