Trans-ethnic Meta-analysis of White Blood Cell Phenotypes.

Publication Type:

Journal Article

Source:

Human molecular genetics, Volume 23, Issue 25, p.6944-60 (2014)

Keywords:

2014, 258, August 2014, Public Health Sciences Division, Scientific Imaging Core Facility

Abstract:

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior GWAS meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50,000 individuals from three diverse populations (Japanese, African-American, and European-ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil, and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine map the putatively causal variants within loci. Lastly, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis, and 9 secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.