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Chunk #18 — Results — Association Analysis in Individuals with Endophenotype Data

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In search of rare variants: preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes.
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In order to evaluate whether the aggregate effect of rare nonsynonymous variants in genes produced associations with the endophenotypes, we conducted burden tests using a variable threshold count-based method (Price et al., 2010) to group nonsynonymous variants within genes. Variants were annotated using EPACTS (Kang, 2014) against GENCODE v11. All missense and nonsense nonsynonymous SNPs, including essential splice SNPs, were included in all gene-based tests. Depending on the phenotype, we tested from 15,816 (P3 genetic factor) to 16,394 (antisaccade) genes that had at least two nonsynonymous variants and a burden allele count of at least three, considering only variants with MAF < .05, resulting in Bonferroni corrections of ~3.2 × 10−6. No gene was associated with any endophenotype at these levels of significance.