Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).
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.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ccarty@fhcrc.org
Cara L
CL
Carty
Nicholas A
NA
Johnson
Carolyn M
CM
Hutter
Alexander P
AP
Reiner
Ulrike
U
Peters
Hua
H
Tang
Charles
C
Kooperberg
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001827:Body Height / Q000208:ethnology / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide