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. 2010 Jul 1;19(13):2725-38.
doi: 10.1093/hmg/ddq154. Epub 2010 Apr 16.

Genome-wide association of anthropometric traits in African- and African-derived populations

Sun J Kang  1 , Charleston W K Chiang, Cameron D Palmer, Bamidele O Tayo, Guillaume Lettre, Johannah L Butler, Rachel Hackett, Adebowale A Adeyemo, Candace Guiducci, Ilze Berzins, Thutrang T Nguyen, Tao Feng, Amy Luke, Daniel Shriner, Kristin Ardlie, Charles Rotimi, Rainford Wilks, Terrence Forrester, Colin A McKenzie, Helen N Lyon, Richard S Cooper, Xiaofeng Zhu, Joel N Hirschhorn
Affiliations

Genome-wide association of anthropometric traits in African- and African-derived populations

Sun J Kang et al. Hum Mol Genet. .

Abstract

Genome-wide association (GWA) studies have identified common variants that are associated with a variety of traits and diseases, but most studies have been performed in European-derived populations. Here, we describe the first genome-wide analyses of imputed genotype and copy number variants (CNVs) for anthropometric measures in African-derived populations: 1188 Nigerians from Igbo-Ora and Ibadan, Nigeria, and 743 African-Americans from Maywood, IL. To improve the reach of our study, we used imputation to estimate genotypes at approximately 2.1 million single-nucleotide polymorphisms (SNPs) and also tested CNVs for association. No SNPs or common CNVs reached a genome-wide significance level for association with height or body mass index (BMI), and the best signals from a meta-analysis of the two cohorts did not replicate in approximately 3700 African-Americans and Jamaicans. However, several loci previously confirmed in European populations showed evidence of replication in our GWA panel of African-derived populations, including variants near IHH and DLEU7 for height and MC4R for BMI. Analysis of global burden of rare CNVs suggested that lean individuals possess greater total burden of CNVs, but this finding was not supported in an independent European population. Our results suggest that there are not multiple loci with strong effects on anthropometric traits in African-derived populations and that sample sizes comparable to those needed in European GWA studies will be required to identify replicable associations. Meta-analysis of this data set with additional studies in African-ancestry populations will be helpful to improve power to detect novel associations.

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Figures

Figure 1.
Figure 1.
QQ plots for height and BMI in GWA results in the African-American cohort, the Nigerian cohort and the meta-analysis. For height and BMI, respectively, the GC inflation factors = 1.03 and 1.02 in the African-American cohort and 1.12 and 1.10 in the Nigerian cohorts. Studies were individually corrected for GCI (λ) prior to meta-analysis, but not again after meta-analysis. After meta-analysis, the λ's are 1.00 and 0.99, respectively.
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