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Chunk #63 — Methods — SNP-based heritability (h2)

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Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals.
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SNP-based h2 for common SNPs mapped to HapMap3 was estimated in EUR, AFR and LA ancestries using LD Score regression (LDSC)75; corresponding populations in the 1000 Genomes Project phase 3 were used as LD reference panels. For PAU in EUR, we only estimated the observed-scale h2. For AUD, both observed-scale h2 and liability-scale h2 were estimated, using population lifetime prevalence estimates of 0.326, 0.220 and 0.229 in EUR, AFR and LA, respectively2. These prevalence estimates were for lifetime DSM-5 AUD in the United States, which could introduce bias given the different definitions and prevalence in different cohorts. By default, LDSC removes SNPs with sample size <90th percentile N/2. Here, we skipped this filtering and kept all SNPs for analyses because we did basic filtering based on the number of cohorts and sample size. The final number of SNPs in the analyses ranged from 527,994 to 1.17M.