GWAS results from the four cohorts were combined using inverse variance weighted meta-analysis in METAL (http://www.sph.umich.edu/csg/abecasis/metal/). Meta-analysis was performed on approximately 2,534,500 SNPs after applying genomic control for each study and filtering SNPs with extremely low imputation quality ratios (<0.01) and MAF (<1%). The genome-wide significance threshold was defined a priori as P<5×10−8, the Bonferroni adjustment for one million independent tests75. Information on SNP function and position relative to genes, microRNA, and transcription factor binding sites was obtained using a Perl script (J.B.W.) that queries tables of the UCSC genome browser15 (hg18, March 2006 genome build). Functional effects of non-synonymous SNPs on protein structure and function were predicted using PolyPhen17.
