PMID- 23696099
OWN - NLM
STAT- MEDLINE
DCOM- 20131101
LR  - 20221207
IS  - 2160-1836 (Electronic)
IS  - 2160-1836 (Linking)
VI  - 3
IP  - 7
DP  - 2013 Jul 8
TI  - Genetic variants that confer resistance to malaria are associated with red blood 
      cell traits in African-Americans: an electronic medical record-based genome-wide 
      association study.
PG  - 1061-8
LID - 10.1534/g3.113.006452 [doi]
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 x 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 < 5 x 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.
FAU - Ding, Keyue
AU  - Ding K
AD  - Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, 
      USA.
FAU - de Andrade, Mariza
AU  - de Andrade M
FAU - Manolio, Teri A
AU  - Manolio TA
FAU - Crawford, Dana C
AU  - Crawford DC
FAU - Rasmussen-Torvik, Laura J
AU  - Rasmussen-Torvik LJ
FAU - Ritchie, Marylyn D
AU  - Ritchie MD
FAU - Denny, Joshua C
AU  - Denny JC
FAU - Masys, Daniel R
AU  - Masys DR
FAU - Jouni, Hayan
AU  - Jouni H
FAU - Pachecho, Jennifer A
AU  - Pachecho JA
FAU - Kho, Abel N
AU  - Kho AN
FAU - Roden, Dan M
AU  - Roden DM
FAU - Chisholm, Rex
AU  - Chisholm R
FAU - Kullo, Iftikhar J
AU  - Kullo IJ
LA  - eng
GR  - UL1 TR000150/TR/NCATS NIH HHS/United States
GR  - U01-HG-04603/HG/NHGRI NIH HHS/United States
GR  - U01 HG004603/HG/NHGRI NIH HHS/United States
GR  - U01HG004609/HG/NHGRI NIH HHS/United States
GR  - U01 HG004609/HG/NHGRI NIH HHS/United States
GR  - U01 HG004599/HG/NHGRI NIH HHS/United States
GR  - U01-HG-06379/HG/NHGRI NIH HHS/United States
GR  - U01 HG006378/HG/NHGRI NIH HHS/United States
GR  - R01 GM105688/GM/NIGMS NIH HHS/United States
GR  - U01 HG006379/HG/NHGRI NIH HHS/United States
GR  - U01-HG-04599/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130708
PL  - England
TA  - G3 (Bethesda)
JT  - G3 (Bethesda, Md.)
JID - 101566598
RN  - 0 (Hemoglobins)
SB  - IM
MH  - Black or African American/*genetics
MH  - Disease Resistance/*genetics
MH  - Electronic Health Records
MH  - Erythrocyte Count
MH  - Erythrocyte Indices/genetics
MH  - Erythrocytes/*pathology
MH  - *Genome-Wide Association Study
MH  - Hematocrit
MH  - Hemoglobins/genetics
MH  - Humans
MH  - Malaria/blood/*genetics
PMC - PMC3704235
OTO - NOTNLM
OT  - African-Americans
OT  - electronic medical record
OT  - genome-wide association study
OT  - informatics
OT  - natural selection
OT  - red blood cell (RBC) traits
EDAT- 2013/05/23 06:00
MHDA- 2013/11/02 06:00
PMCR- 2013/07/01
CRDT- 2013/05/23 06:00
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2013/11/02 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - g3.113.006452 [pii]
AID - GGG_006452 [pii]
AID - 10.1534/g3.113.006452 [doi]
PST - epublish
SO  - G3 (Bethesda). 2013 Jul 8;3(7):1061-8. doi: 10.1534/g3.113.006452.