Gene-based analyses was performed with “multi-marker analysis of genomic annotation” (MAGMA, version 1.08)27 (Supplementary Information sections 6.1.2). Genome-wide SNPs were first mapped to 18,235 protein-coding genes from Ensembl (build 85)84, and SNPs within each gene were jointly tested for association with EXT. We evaluated Bonferroni-corrected significance, adjusted for the number of genes (one-sided P < 2.74×10−6) (Supplementary Table 13). Next, MAGMA gene-set analysis was performed using 15,481 curated gene sets and Gene Ontology (GO)85 terms obtained from the Molecular Signatures Database (MsigDB version 7.0)86. We evaluated Bonferroni-corrected significance, adjusted for the number of gene sets (one-sided P < 3.23×10−6) (Supplementary Table 14). A gene property analysis tested the relationships between 54 tissue-specific gene expression profiles and gene associations, while adjusting for the average expression of genes per tissue type as a covariate (Supplementary Table 15), and between brain gene expression profiles and gene associations across 11 brain tissues from BrainSpan87 (Supplementary Table 16). Gene expression values were log2 transformed average Reads Per Kilobase Million (RPKM) per tissue type (after replacing RPKM > 50 with 50) based on GTEx RNA-seq data (version 8.0)88. We evaluated Bonferroni-corrected significance, adjusted for the number of tested profiles (one-sided P < 9.26×10−4).
