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Activity Number: 299 - SPEED: Recent Advances in Statistical Genomics and Genetics
Type: Contributed
Date/Time: Tuesday, July 31, 2018 : 8:30 AM to 10:20 AM
Sponsor: Section on Statistics in Genomics and Genetics
Abstract #329345
Title: ProxECAT: Proxy External Controls Association Test. a New Case-Control Gene Region Association Test Using Allele Frequencies from Public Controls
Author(s): Audrey Hendricks* and Stephen Billups and Hamish Pike and Eleftheria Zeggini and Stephanie Santorico and InĂªs Barroso and Josee Dupuis
Companies: University of Colorado - Denver and University of Colorado - Denver and University of Colorado-Aschutz Medical Campus and Wellcome Trust Sanger Institute and University of Colorado - Denver and Wellcome Trust Sanger Institute and Boston University School of Public Health
Keywords: external controls; public controls; sequencing; rare variant; case-control; ProxECAT

Power for rare-variant case-control studies can be increased by leveraging existing resources, such as the Exome Aggregation Consortium (ExAC; >60,000 exomes). These resources are underutilized due to potential for considerable bias caused by differences in sequencing technology, processing, and read depth. To address this need, we have developed ProxECAT (Proxy External Controls Association Test), a closed form test that estimates enrichment of rare variants within a gene region using internally sequenced cases and external controls. We present results from a variety of simulations and application to a UK10K dataset of 926 whole-exome sequenced cases (~80x) and either 3,621 whole-genome sequenced controls (~7x) or ExAC controls. ProxECAT maintains the expected type I error. Specifically, when we simulate cases to have 20%-50% more rare variants compared to controls, the type I error increases to >10%-30% for traditional case-control tests while our method maintains the expected 5% type I error. Since ProxECAT uses exclusively external controls, resources can be devoted to sequencing cases resulting in greater power for ProxECAT compared to case-control tests.

Authors who are presenting talks have a * after their name.

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