and a plethora of comorbid traits in the Yale-Penn sample, than FTND PGS. The only exception was for smoke after waking, which was more strongly associated with FTND PGS, likely because time-to-first cigarette is one of the FTND items. TUD was highly correlated (rg=0.81) with regular cigarette use (i.e., smoking at least 100 cigarettes in a lifetime, previously referred to as “smoking initiation”)13, which is expected as nicotine is a highly addictive substance, with 85% of smokers meeting criteria for TUD.1,2 However, our polygenic findings demonstrate that TUD explains additional variance above and beyond that accounted for by other smoking traits (smoking initiation, CPD, FTND). This emphasizes the need to measure the full spectrum of addiction liability,49 from regular use to more severe phenotypes, such as TUD, to account for the distinct biological factors relevant at each stage.
