Gene annotation, gene-based test statistics and pathway analysis were performed using the KGG2.5 software package42 (Supplementary Table 7 and Extended Data Fig. 7). Linkage disequilibrium was calculated based on RSID numbers using the 1000 Genomes Project European samples as a reference (http://enigma.ini.usc.edu/protocols/genetics-protocols/). For the annotation, SNPs were considered ‘within’ a gene if they fell within 5 kb of the 3′/5′ untranslated regions based on human genome (hg19) coordinates. Gene-based tests were performed using the GATES test42 without weighting P values by predicted functional relevance. Pathway analysis was performed using the hybrid set-based test (HYST) of association43. For all gene-based tests and pathway analyses, results were considered significant if they exceeded a Bonferroni correction threshold accounting for the number of pathways and traits tested such that Pthresh = 0.05/(671 pathways × 7 independent traits) = 1.06 × 10−5.
