Sex and generation shape the genetic architecture of smoking initiation

The rapidly changing cultural contexts over the past century modified the genetic factors that influence smoking initiation (SI). Using data from nearly seven million respondents, we conducted genome-wide associations study (GWAS) meta-analyses stratified by sex and generation across European, East Asian, African American, and Latino genetic ancestry populations. Sex and generation, but not genetic ancestry, moderate both the SNP-based heritability estimates and associations with individual loci. Specifically, SI is more heritable in females and younger generations. Furthermore, the impact of

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