Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.

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dc.contributor.authorOtieno, F. G.
dc.contributor.authorLanktree, M.B.
dc.contributor.authorGuo, Y.
dc.contributor.authorMurtaza, M.
dc.contributor.authorGlessner, J.T.
dc.date.accessioned2014-11-18T09:50:55Z
dc.date.available2014-11-18T09:50:55Z
dc.date.issued2011
dc.description.abstractHeight is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.en_US
dc.identifier.citationAmerican Journal of Human Genetics 2011 Jan 7;88(1):6-18. doi: 10.1016/j.ajhg.2010.11.007.en_US
dc.identifier.issn0002-9297
dc.identifier.other1537-6605
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014369/pdf/main.pdf
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/11694
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.titleMeta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.en_US
dc.typeArticleen_US
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