[PDF][PDF] Bias in estimates of quantitative-trait–locus effect in genome scans: demonstration of the phenomenon and a method-of-moments procedure for reducing bias

DB Allison, JR Fernandez, M Heo, S Zhu… - The American Journal of …, 2002 - cell.com
DB Allison, JR Fernandez, M Heo, S Zhu, C Etzel, TM Beasley, CI Amos
The American Journal of Human Genetics, 2002cell.com
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 …
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.
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