Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster.

Journal Article (Journal Article;Multicenter Study)

In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or beta thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E-08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression.

Full Text

Duke Authors

Cited Authors

  • Solovieff, N; Milton, JN; Hartley, SW; Sherva, R; Sebastiani, P; Dworkis, DA; Klings, ES; Farrer, LA; Garrett, ME; Ashley-Koch, A; Telen, MJ; Fucharoen, S; Ha, SY; Li, C-K; Chui, DHK; Baldwin, CT; Steinberg, MH

Published Date

  • March 4, 2010

Published In

Volume / Issue

  • 115 / 9

Start / End Page

  • 1815 - 1822

PubMed ID

  • 20018918

Pubmed Central ID

  • PMC2832816

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-08-239517


  • eng

Conference Location

  • United States