An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

ABSTRACT: Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutati

SUBMITTER: Werling DM 

PROVIDER: S-EPMC5961723 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature