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Activity Number: 241
Type: Contributed
Date/Time: Monday, July 30, 2012 : 2:00 PM to 3:50 PM
Sponsor: Biometrics Section
Abstract - #304187
Title: Higher Criticism for Detecting Sparse and Weak Genetic Effects
Author(s): Zheyang Wu*+
Companies: WPI
Address: 100 Institute Road, Worcester, MA, 01609, United States
Keywords: GWAS ; higher criticism ; hypothesis testing ; regression model ; detection boundary ; gene-based method

Genome-wide association studies (GWAS) have identified many genetic factors underlying complex traits. However, these factors only explained a small fraction of genetic contributions to these traits. The remaining factors are weak at the population level and distribute sparsely across the genome. We adapt the recent innovation of Higher Criticism to SNP-set analysis of GWAS, and develop new theoretic framework in large-scale inference to assess the joint significances of such sparse and weak effect for a quantitative trait. We discover a detection boundary to quantify the effect rarity and effect strength. Above the boundary, the overall effects of genetic factors are strong enough and allow for reliable detection. Below the detection boundary, the genetic factors are simply too rare and weak so that reliable detection is impossible. We show that the HC-type methods are optimal in that they yield reliably detection once the parameters of the genetic effects fall above the detection boundary, and that many commonly used SNP-set methods are not optimal. The superior performance of the HC-type method is demonstrated through simulations and the analysis of Crohn's disease GWAS data.

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