title: Bias in estimates of quantitative-trait-locus effect in genome scans: demonstration of the phenomenon and a method-of-moments procedure for reducing bias.
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.
authors.affiliation: Department of Biostatistics and Center for Research on Clinical Nutrition, University of Alabama at Birmingham, 35294-0022, USA. Dallison@ms.soph.uab.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
authors.forename: Moonseong
authors.initials: M
authors.lastname: Heo
authors.forename: Shankuan
authors.initials: S
authors.lastname: Zhu
authors.forename: Carol
authors.initials: C
authors.lastname: Etzel
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
mesh_terms: D015982:Bias; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D009010:Monte Carlo Method; D009765:Obesity / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results; D009626:Terminology as Topic