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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.

TitleExome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.
Publication TypeJournal Article
Year of Publication2016
AuthorsChami N, Chen M-H, Slater AJ, et al.
Secondary AuthorsLettre G
JournalAm J Hum Genet
Volume99
Issue1
Pagination8-21
Date Published2016 Jul 07
ISSN1537-6605
KeywordsAfrican Americans, Allelic Imbalance, Erythrocyte Indices, Erythrocytes, Erythropoiesis, Exome, Gene Frequency, Genetic Pleiotropy, Genetic Variation, Genotype, Hematocrit, Hemoglobins, Humans, Quantitative Trait Loci
Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p

DOI10.1016/j.ajhg.2016.05.007
Alternate JournalAm J Hum Genet
PubMed ID27346685
PubMed Central IDPMC5005438
Grant ListR01 HL112064 / HL / NHLBI NIH HHS / United States
R01 DK060022 / DK / NIDDK NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL107816 / HL / NHLBI NIH HHS / United States
R01 HL122684 / HL / NHLBI NIH HHS / United States
P30 DK056341 / DK / NIDDK NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
S10 OD018522 / OD / NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HD074711 / HD / NICHD NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
R01 DK033301 / DK / NIDDK NIH HHS / United States
R21 HL121429 / HL / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
R21 HL121422 / HL / NHLBI NIH HHS / United States