biostudies-literatureOjewunmi OOKing's College Hospital CharityNIHR Oxford BRCWellcome Trust CoreLIBRAMedical Research CouncilNHLBI NIH HHSSickle Pan-Africa Research Consortium Nigeria NEtworkEPSRCUCL Global Engagement FundsNIHWellcome Trust919-929https://www.ebi.ac.uk/biostudies/studies/S-EPMC11070134biostudies-literatureUnknown33(10)The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, β = -0.39, P = 4.96 × 10-34) and HBS1L-MYB (lead SNP rs61028892, β = 0.73, P = 1.18 ×Human molecular geneticsThe genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.PMC11070134203141/Z/16/ZMR/T013389/1EP/X527920/12016/17U01 HL1569421U01HL156942–01-02Inyang BIsa HAdebiyi NMMkumbe BSAdeyemo TAOyetunji AIUmar IAKang GFaruk JAGrace CInusa BPDJamoh BYHassan AOjewunmi OOPatel HAhmad HRBrewin JAkinrindoye AEkong RGoel AChung RLee SHRashkin SNnodu OChianumba RNkya SStrouboulis JGardner KRooks HMenzel SMwita LMakani JAgumadu UNSangeda RFalchi MfalseThe genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, β = -0.39, P = 4.96 × 10-34) and HBS1L-MYB (lead SNP rs61028892, β = 0.73, P = 1.18 ×2024-01-01T00:00:00Z2024 May2026-05-29T17:47:15.729Z2025-08-17T03:05:45.288ZS-EPMC110701343833999510.1093/hmg/ddae014