Sex and generation shape the genetic architecture of smoking initiation

Smoking initiation is more heritable in females and younger generations, with sex and generation moderating SNP heritability and locus associations across nearly seven million respondents.

• Why it matters: Genetic influences on smoking initiation likely shift as cultural and policy contexts change, but it is unclear how sex and generational timing reshape the underlying genetic architecture.
• What they did: The study ran GWAS meta-analyses stratified by sex and generation across European, East Asian, African American, and Latino ancestry groups, then assessed moderated heritability, cross-trait genetic correlations, heterogeneity, and finemapping.
• The result: It identified 1,717 SI-associated loci, including 45 sex-specific and 7 generation-specific loci, and finemapped 389 and 304 loci with distinct potential causal-variant patterns by sex and generation.

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