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


ABSTRACT: 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.

SUBMITTER: Shriner D 

PROVIDER: S-EPMC2792725 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

Shriner Daniel D   Adeyemo Adebowale A   Gerry Norman P NP   Herbert Alan A   Chen Guanjie G   Doumatey Ayo A   Huang Hanxia H   Zhou Jie J   Christman Michael F MF   Rotimi Charles N CN  

PloS one 20091222 12


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 w  ...[more]

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