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Rare CHRNB3 Variant Linked to Much Lower Cigarette Use, With Cross-Ancestry Evidence

Experts urge cautious follow-up before pursuing therapies that inhibit the β3 nicotinic receptor.

Overview

  • Genome sequencing of 37,897 current smokers in Mexico City identified a CHRNB3 p.Glu284Gly variant concentrated in people of Indigenous Mexican ancestry.
  • Carriers smoked about 21% fewer cigarettes per day with one copy of the variant and roughly 78% fewer with two copies.
  • Independent analyses in UK Biobank and Biobank Japan showed convergent CHRNB3 signals with similar effect directions across European and East Asian cohorts.
  • The genetic effects appear to influence smoking intensity rather than whether people start smoking, and the underlying mechanism remains unclear.
  • Researchers and outside experts call for laboratory studies, detailed phenotyping, larger cohorts, and scrutiny of conflicts related to Regeneron ties and patent claims.