Several secondary analyses support our findings. First, we applied cross validation in the nine samples to examine the internal consistency of the results. We created sub-samples by iteratively removing the data of each of the individual samples and conducting meta-analysis with the remaining datasets. A highly significant proportion of the top results were consistently identified across these sub-analyses, suggesting the stability and validity of our findings. Next we estimated the genome-wide contribution via GREML and the complementary LD-score regression approach, producing generally consistent estimates of SNP heritability across samples included and methods applied. Similar to GWAS studies of many phenotypes (36), these estimates are substantially smaller than those predicted by twin studies of ADs. Finally, we tested the polygenic association between our results and those from other psychiatric disorders using GRPS, finding significant correlation of genetic risk between ADs and MDD but not between ADs and BIP or SCZ. The former result is consistent with large epidemiologic studies that report correlated genetic risk between ADs and MDD (see (15) for review) as well as a prior overlap seen for depression and anxiety scales (37).
