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LOD score exclusion analyses for candidate genes using random population samples

LOD score exclusion analyses for candidate genes using random population samples While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes with random population samples. We develop a LOD score approach for exclusion analyses of candidate genes with random population samples. Under this approach, specific genetic effects and inheritance models at candidate genes can be analysed and if a LOD score is ≤− 2.0, the locus can be excluded from having an effect larger than that specified. Computer simulations show that, with sample sizes often employed in association studies, this approach has high power to exclude a gene from having moderate genetic effects. In contrast to regular association analyses, population admixture will not affect the robustness of our analyses; in fact, it renders our analyses more conservative and thus any significant exclusion result is robust. Our exclusion analysis complements association analysis for candidate genes in random population samples and is parallel to the exclusion mapping analyses that may be conducted in linkage analyses with pedigrees or relative pairs. The usefulness of the approach is demonstrated by an application to test the importance of vitamin D receptor and estrogen receptor genes underlying the differential risk to osteoporotic fractures. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

LOD score exclusion analyses for candidate genes using random population samples

DENG, H.‐W.; LI, J.; RECKER, R. R.
Annals of Human Genetics , Volume 65 (3) – Jan 1, 2001
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References (49)

Publisher
Wiley
Copyright
Copyright © 2001 Wiley Subscription Services
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1046/j.1469-1809.2001.6530313.x
Publisher site
See Article on Publisher Site

Abstract

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes with random population samples. We develop a LOD score approach for exclusion analyses of candidate genes with random population samples. Under this approach, specific genetic effects and inheritance models at candidate genes can be analysed and if a LOD score is ≤− 2.0, the locus can be excluded from having an effect larger than that specified. Computer simulations show that, with sample sizes often employed in association studies, this approach has high power to exclude a gene from having moderate genetic effects. In contrast to regular association analyses, population admixture will not affect the robustness of our analyses; in fact, it renders our analyses more conservative and thus any significant exclusion result is robust. Our exclusion analysis complements association analysis for candidate genes in random population samples and is parallel to the exclusion mapping analyses that may be conducted in linkage analyses with pedigrees or relative pairs. The usefulness of the approach is demonstrated by an application to test the importance of vitamin D receptor and estrogen receptor genes underlying the differential risk to osteoporotic fractures.

Journal

Annals of Human Genetics – Wiley

Published: Jan 1, 2001

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