Name: sabatti

Firstname: chiara

Title: assistant professor

Institution: UCLA

Street: 695 c. Young Dr. South

City: Los Angels

Zip-Code: 90095-7088

Country: USA

Phone: 310 794 9567

Fax: 310 794 5446

Email: csabatti@mednet.ucla.edu

Authors: Chiara Sabatti, Susan Service, Nelson Freimer

Title: False Discovery Rate and Correction for Multiple Comparisons in Linkage Disequilibrium Genome Screens

Abstract: Population based linkage disequilibrium genome screen represent one of the most recent approaches for the localization of disease genes. One open problem in this context is represented by the definition of an appropriate significance threshold that takes into account the multiple comparison problem. We explore the conceptual and practical implications of the multiple testing procedure known as False Discovery Rate (FDR). We argue that controlling the FDR better represents the interest of researcher in this area than more traditional approaches. We then explore the applicability of the Benjamini-Hochberg FDR controlling procedure in the specific context of association mapping from case-control data. We analyze the nature of dependency between the test statistics with analytic work and simulations and we conclude that the BH rule effectively controls FDR in our context of interest. The dependency between test statistics translates in a decrease of power, which suggest the opportunity of developing resampling based rules to control FDR.

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