Testing associations on the level of protein-coding genes can be more biologically meaningful and is more powerful (lower multiple testing burden) than testing solely on the level of SNPs. Gene-based analysis was used to test associations for the combined effect of SNPs in protein-coding genes taking into account LD between the SNPs and the size of the gene. The analysis was conducted in MAGMA (v 1.6) 25, which uses the 1000 Genomes reference-panel (phase 3, 2012) to control for LD. SNPs were mapped to genes if they were located in or within 10 kb from the gene, such that 5,710,956 SNPs (49%) could be mapped to at least one of 18,293 protein-coding genes in the reference panel. The significance threshold was set at p<2.74e-06 (Bonferroni corrected p-value for 18,293 tests).
