Genetic study implicates BACH2-NRF2 axis in fetal haemoglobin activation
A multi-ancestry study of 28,279 individuals identified 91 conditionally independent associations for fetal haemoglobin (HbF) levels across 12 genomic regions. In one previously uncharacterized region, the causal variant rs1010474-C reduces BACH2 expression and elevates HbF. Inhibiting BACH2 directly likewise increases HbF. Loss of BACH2 enhances NRF2 chromatin occupancy at the γ-globin genes, which encode HbF. Although their binding motifs overlap, selective editing can switch γ-globin on or off independently of BCL11A.
Teams developing therapies that raise fetal haemoglobin gain a genetically supported pathway to study, though these findings detail regulatory mechanisms rather than a treatment.
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