LOD score exclusion analyses for candidate genes using random population samples

Citation
Hw. Deng et al., LOD score exclusion analyses for candidate genes using random population samples, ANN HUM GEN, 65, 2001, pp. 313-329
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
ANNALS OF HUMAN GENETICS
ISSN journal
0003-4800 → ACNP
Volume
65
Year of publication
2001
Part
3
Pages
313 - 329
Database
ISI
SICI code
0003-4800(200105)65:<313:LSEAFC>2.0.ZU;2-E
Abstract
While extensive analyses have been conducted to test for, no formal analyse s have been conducted to test against, the importance of candidate genes wi th random population samples. We develop a LOD score approach for exclusion analyses of candidate genes with random population samples. Under this app roach, specific genetic effects and inheritance models at candidate genes c an be analysed and if a LOD score is less than or equal to -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 stud ies, this approach has high power to exclude a gene from having moderate ge netic effects. In contrast to regular association analyses, population admi xture will not affect the robustness of our analyses; in fact, it renders o ur analyses more conservative and thus any significant exclusion result is robust. Our exclusion analysis complements association analysis for candida te genes in random population samples and is parallel to the exclusion mapp ing analyses that may be conducted in linkage analyses with pedigrees or re lative pairs. The usefulness of the approach is demonstrated by an applicat ion to test the importance of vitamin D receptor and estrogen receptor gene s underlying the differential risk to osteoporotic fractures.