Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).

Publication Type:

Journal Article

Source:

Human molecular genetics, Volume 21, Issue 3, p.711-720 (2012)

Keywords:

2012, Center-Authored Paper, Consortium Authored Paper, Nov 11, November 2011, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility

Abstract:

Height is a complex trait under strong genetic influence. To date, numerous genetic loci have been associated with height in individuals of European ancestry. However, few large-scale discovery genome-wide association studies (GWAS) of height in minority populations have been conducted and thus information about population-specific height regulation is limited. We conducted a GWA analysis of height in 8149 African-American (AA) women from the Women's Health Initiative. Genetic variants with P< 5 × 10(-5) (n = 169) were followed up in a replication data set (n = 20 809) and meta-analyzed in a total of 28 958 AAs and African-descent individuals. Twelve single-nucleotide polymorphisms (SNPs) representing 7 independent loci were significantly associated with height at P < 5 × 10(-8). We identified novel SNPs in 17q23 (TMEM100/PCTP) and Xp22.3 (ARSE) reflecting population-specific regulation of height in AAs and replicated five loci previously reported in European-descent populations [4p15/LCORL, 11q13/SERPINH1, 12q14/HMGA2, 17q23/MAP3K3 (mitogen-activated protein kinase3) and 18q21/DYM]. In addition, we performed an admixture mapping analysis of height which is both complementary and supportive to the GWA analysis and suggests potential associations between ancestry and height on chromosomes 4 (4q21), 15 (15q26) and 17 (17q23). Our findings provide insight into the genetic architecture of height and support the investigation of non-European-descent populations for identifying genetic factors associated with complex traits. Specifically, we identify new loci that may reflect population-specific regulation of height and report several known height loci that are important in determining height in African-descent populations.