All variants within 500 kb (HapMap release 22/1000 Genomes CEU) and in LD (r2 > 0.7) with an index SNP were annotated for functional effects based on RefSeq transcripts using Annovar43 (http://www.openbioinformatics.org/annovar/). PhastCon, Grantham, GERP, and PolyPhen44 predictions were accessed via the Exome Variant Server45 (http://evs.gs.washington.edu/EVS), and from SIFT46 (http://sift.jcvi.org/) (Extended Data Table 4).
