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Am J Hum Genet. 2000 Jul;67(1):249-52. Epub 2000 May 11.

Testing the robustness of the new Haseman-Elston quantitative-trait loci-mapping procedure.

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  • 1Obesity Research Center, St. Luke's/Roosevelt Hospital, Columbia University College of Physicians & Surgeons, New York, NY 10025, USA. dba8@columbia.edu


Variance components (VC) techniques have emerged as among the more powerful methods for detection of quantitative-trait loci (QTL) in linkage analysis. Allison et al. found that, with particularly marked leptokurtosis in the phenotypic distribution and moderate-to-high residual sibling correlation, maximum likelihood (ML) VC methods may produce a severe excess of type I errors. The new Haseman-Elston (NHE) method is a least-squares-based VC method for mapping of QTL in sib pairs (Elston et al.). Using simulation, we investigate the robustness of the NHE to marked nonnormality, by means of the same distributions and worst-case conditions identified by Allison et al. for the ML approach (i.e., 100 pairs; high residual sibling correlation). Results showed that, when marked nonnormality is present, the NHE can be used without severe type I error-rate inflation, even at very small alpha levels.

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