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Chunk #19 — Method — Heritability Due to Rare Variants

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Rare nonsynonymous exonic variants in addiction and behavioral disinhibition.
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Genome-wide Complex Trait Analysis (GCTA) is a method to calculate the phenotypic variance accounted for by all SNPs in aggregate. Genetic relationships among all unrelated individuals in a sample are used in a mixed model to account for variance in the phenotype of interest. While GCTA has been applied regularly to common SNPs(1), including reports for the phenotypes in this sample(9), to our knowledge its application has not been extended to rare exonic variants. Further, since the sample is also genotyped on a genome-wide array, we were able to compare multiple marker sets: the set of all rare (MAF<.05) nonsynonymous variants; the set of all common variants (MAF≥.05), regardless of annotation.