Conventional “clumping” was applied with PLINK (v1.90b6.13)67 to identify near-independent genome-wide significant lead SNPs, with the primary (two-sided) P-value threshold of 5×10−8, the secondary P-value threshold (for computational efficiency) of 1×10−4, and an r2 threshold of 0.1 together with a wide SNP window (1,000,000 kb). Before counting the number of hits to report, we first subjected the 855 lead SNPs to “multi-SNP-based conditional & joint association analysis using GWAS summary data” (GCTA-COJO, version 1.93.1beta)23,68 (Supplementary Information section 3.4.2). This procedure identified 579 lead SNPs that were conditionally and jointly associated with EXT (Supplementary Table 9). We performed lookups of these “579 EXT SNPs”, and any correlated SNPs (r2 > 0.1), in the NHGRI-EBI GWAS Catalog6 (e96 2019-05-03) to investigate whether the loci have previously reported with other traits (at two-sided P < 1×10−5) (Supplementary Table 10). To evaluate whether each SNP acted through the externalizing factor, we estimated QSNP heterogeneity statistics genome-wide with Genomic SEM (Supplementary Information section 3.5.1). The null hypothesis of the QSNP test is that SNP effects on the constituent phenotypes operate (i.e., are statistically mediated) via
