The polygenic risk score, comprised of the top genetic variants (P-value <5 × 10−7) from the STOMP replicated in the DNHS, accounted for ∼3% of the total variance in cigarette-use frequency. In the current literature, polygenic risk scores typically account for 0.5–4% of the variance in a complex behavioral trait.7, 8 Post hoc analyses indicated that the effect of the polygenic score was largely driven by the effect of CHRNA5 SNP rs203652, the only genetic variant reaching genome-wide significance in the STOMP; however, the addition of the five other variants significantly increased the total variance ∼0.8% in smoking accounted for the GRS (Supplementary Table 1). There are growing numbers of studies that have found an association between a variant in CHRNA5 and smoking phenotypes in diverse populations.48 However, this SNP accounted for ∼0.2% of the phenotypic variance of CPD in the African American STOMP meta-analysis, while a correlated SNP (rs1051730 A allele) accounted for 0.5% of the phenotypic variance in smoking quantity in populations of European ancestry.18 Evidence from animal and magnetic resonance imaging studies support these findings; a study
