Variance calculations for identity-by-descent estimation

Abstract

Nonparametric linkage strategies often involve estimation of identity by descent (IBD) with the use of affected sibling pairs. Methods for IBD estimation are well established and have been successful for mapping complex traits. However, the majority of linkage approaches involving IBD have focused on statistical testing, rather than on the effect estimates themselves. Through a bootstrap procedure developed for linkage-scan data sets, we provide standard errors for the estimated mean IBD that are broadly applicable. Applications that benefit from the availability of standard errors include effect-size estimates and confidence intervals; meta-analyses, including tests for heterogeneity; and discordant-sibling-pair evaluation. We demonstrate the use of estimated mean IBD and its standard errors in the National Institute of Mental Health Human Genetics Initiative linkage samples for bipolar disorder and Alzheimer disease. Mean IBD and its standard errors are valuable tools for the further assessment and evaluation of linkage-scan samples involving complex disease. © 2006 by The American Society of Human Genetics. All rights reserved.