TY - JOUR
T1 - Genetic variants that confer resistance to malaria are associated with red blood cell traits in African-Americans
T2 - An electronic medical record-based genome-wide association study
AU - Ding, Keyue
AU - Andrade, Mariza de
AU - Manolio, Teri A.
AU - Crawford, Dana C.
AU - Rasmussen-Torvik, Laura J.
AU - Ritchie, Marylyn D.
AU - Denny, Joshua C.
AU - Masys, Daniel R.
AU - Jouni, Hayan
AU - Pachecho, Jennifer A.
AU - Kho, Abel N.
AU - Roden, Dan M.
AU - Chisholm, Rex
AU - Kullo, Iftikhar J.
PY - 2013/7
Y1 - 2013/7
N2 - To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria-HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)-were associated (P ≤ 1 × 10-6) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 1 × 10-8) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/ A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.
AB - To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria-HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)-were associated (P ≤ 1 × 10-6) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 1 × 10-8) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/ A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.
KW - African-Americans
KW - Association study
KW - Electronic medical
KW - Genome-wide
KW - Informatics
KW - Natural selection
KW - Record
KW - Red blood cell (RBC)
KW - Traits
UR - http://www.scopus.com/inward/record.url?scp=84883213248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883213248&partnerID=8YFLogxK
U2 - 10.1534/g3.113.006452
DO - 10.1534/g3.113.006452
M3 - Article
C2 - 23696099
AN - SCOPUS:84883213248
SN - 2160-1836
VL - 3
SP - 1061
EP - 1068
JO - G3: Genes, Genomes, Genetics
JF - G3: Genes, Genomes, Genetics
IS - 7
ER -