Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans | oneSCDvoice
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scientific articles

Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans

key information

source: Blood

year: 2012

authors: Bae HT, Baldwin CT, Sebastiani P, Telen MJ, Ashley-Koch A, Garrett M, Hooper WC, Bean CJ, Debaun MR, Arking DE, Bhatnagar P, Casella JF, Keefer JR, Barron-Casella E, Gordeuk V, Kato GJ, Minniti C, Taylor J, Campbell A, Luchtman-Jones L, Hoppe C, Gladwin MT, Zhang Y, Steinberg MH

summary/abstract:

Fetal hemoglobin (HbF) protects against many but not all of the hematologic and clinical complications of sickle cell anemia.1,2 This protection is dependent on the ability of HbF to hinder deoxyHbS polymerization. HbF level is variable and highly heritable. Previous genetic association studies found single nucleotide polymorphisms (SNPs) in regions of BCL11A (chromosome 2p), in the HBS1L-MYB intergenic polymorphism (HMIP; chromosome 6q), and linked to HBB (chromosome 11p) that were associated with HbF (reviewed in Akinsheye et al1). Our aim was to perform a meta-analysis of genome-wide association studies (GWAS) to find genetic loci with modest effect sizes that were associated with HbF when a larger sample size was examined.

Common SNPs (585, 563 total) from 7 cohorts totaling 2040 patients were meta-analyzed using the software Meta Analysis Helper (METAL)3 with inverse variance method, where effect estimates are weighted in proportion to their precisions.4 The 7 cohorts included in the meta-analysis are: Cooperative Study of Sickle Cell Disease (CSSCD: n = 841), Multicenter Study of Hydroxyurea (MSH: n = 178), Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) study (n = 73), Comprehensive Sickle Cell Centers Collaborative Data (C-data) project (n = 127), Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Treatment (Walk-PHaSST) trial (n = 181), Duke University Outcome Modifying Genes study (n = 152), and Silent Infarct Transfusion (SIT) trial (n = 488).

organisation: Boston University School of Public Health; Boston University School of Medicine; Duke University School of Medicine, Durham; Centers for Disease Control and Prevention, Atlanta; Vanderbilt University School of Medicine, Nashville; Johns Hopkins University School of Medicine, Baltimore; University of Illinois at Chicago; National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda; University of Michigan Medical School; Children's National Medical Center, Washington, DC; Children's Hospital Research Center Oakland; University of Pittsburgh

DOI: 10.1182/blood-2012-06-432849

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