Bias in estimates of quantitative-trait-locus effect in genome scans: Demonstration of the phenomenon and a method-of-moments procedure for reducing bias

David B. Allison, Jose R. Fernandez, Moonseong Heo, Shankuan Zhu, Carol Etzel, T. Mark Beasley, Christopher I. Amos

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

An attractive feature of variance-components methods (including the Haseman-Elston tests) for the detection of quantitative-trait loci (QTL) is that these methods provide estimates of the QTL effect. However, estimates that are obtained by commonly used methods can be biased for several reasons. Perhaps the largest source of bias is the selection process. Generally, QTL effects are reported only at locations where statistically significant results are obtained. This conditional reporting can lead to a marked upward bias. In this article, we demonstrate this bias and show that its magnitude can be large. We then present a simple method-of-moments (MOM)-based procedure to obtain more-accurate estimates, and we demonstrate its validity via Monte Carlo simulation. Finally, limitations of the MOM approach are noted, and we discuss some alternative procedures that may also reduce bias.

Original languageEnglish (US)
Pages (from-to)575-585
Number of pages11
JournalAmerican Journal of Human Genetics
Volume70
Issue number3
DOIs
StatePublished - Mar 2002

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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