To validate this GRS, we used independent data from the Atherosclerosis Risk in the Communities (ARIC) database37 and the Study of Addiction: Genetics and Environment (SAGE) database, accessed through the NIH database of Genotypes and Phenotypes (dbGaP).38 When a GRS SNP was not available in one of these databases, we selected the closest LD proxy for that SNP to include in the GRS. Among European-descent ARIC participants (n=8,293), each standard deviation (SD) increase in the GRS predicted a 1.45 pack-year increase in lifetime cigarette consumption among individuals who had ever smoked (p<0.001) and a 1.02 cigarette increase in daily consumption among these ever smokers (p<0.001). Replication of the GRS-smoking quantity association in the SAGE database and additional validation analyses testing versions of the GRS that exclude the SNPs rs16969968 and rs6495308 are presented in Supplemental Table 2.
