We performed heritability and genetic correlation analyses using LD score regression(52). The method calculates LD scores from the Haplotype Reference Consortium and the estimation of heritability with these LD scores then follows established methods(53, 54). Heritability was estimated for each trait and partitioned by annotation category and frequency bins. First, we annotated variants on the exome chip based upon gene definitions in RefSeq 1.9, using SEQMINER version 6.0(55). A variant is classified as coding if it belongs to either one of the following categories: nonsynonymous, stop gain, stop loss, and splice. Seven functional categories were considered in the model, including intergenic, intron, common coding (MAF>0.01), rare coding (MAF<0.01), synonymous, and 3’/5’ untranslated regions. We fitted the baseline model with seven categories, and estimated phenotypic variance explained by each category.
