Initial sensitivity to the effects of alcohol has been associated, in the ALSPAC sample (Schuckit et al., 2008a; Schuckit et al., 2008b) among others, with later alcohol misuse and problems, such that individuals less sensitive to alcohol when they begin drinking are at higher risk of later misuse. Evidence from twin and family studies, alongside preliminary findings from gene identification efforts, has suggested that the association may be due in part to genetic influences on sensitivity. In the current study, we meta-analyzed GWAS of initial sensitivity to alcohol, using the first 5 times drinking Self-Rating of the Effects of Alcohol (SRE) scale in two large, population-based samples. Analyses yielded few genome-wide significant findings, and PRS were not consistently associated with SRE in two independent samples. Our limited positive results came from aggregate tests, which indicated moderate heritability (overall h2SNP=0.19, SE=0.10) and support for a role of genes involved in hormone signaling. Initial alcohol sensitivity may be more prominently environmentally influenced than previously thought. However, studies of other behavioral outcomes with heritable components have yielded null results until much larger sample
