The PRS pleiotropy analyses are congruent with the previously-observed genetic overlap between AD and major depression on a population level in European-Americans (Andersen et al., 2017) and on a molecular level in African-Americans (Zhou et al., 2017). The observed positive correlation (nominally significant) between depression and MAXDRINKS and negative correlation between depression and flushing are also internally (directionally) consistent with respect to risk. Since the analysis used summary statistics from depression to predict the alcohol-related phenotypes, the outsize effect of the ALDH2 region in the latter phenotypes would not be expected to be a major confound; indeed, the most significant association between ALDH2 and major depression in the CONVERGE sample is 0.041 (and the smallest p-value in the 2Mb region is 0.0049). ALDH2*rs671 is absent from the CONVERGE dataset, again supporting that the effect is not driven by that marker. The most likely interpretation of these results is that depression and alcohol-related traits share some of their genetic risk in Asian populations, as has been previously shown in European populations (Andersen et al., 2017, Zhou et al., 2017).
