The value of relatives with phenotypes but missing genotypes in association studies for quantitative traits - PubMed (original) (raw)
The value of relatives with phenotypes but missing genotypes in association studies for quantitative traits
Peter M Visscher et al. Genet Epidemiol. 2006 Jan.
Erratum in
- Genet Epidemiol. 2007 Nov;31(7):801
Abstract
The additional statistical power of association studies for quantitative traits was derived when ungenotyped relatives with phenotypes are included in the analysis. It was shown that the extra power is a simple function of the coefficient of additive genetic relationship and the phenotypic correlation coefficient between the genotyped and ungenotyped relatives. For close relatives, such as pairs of fullsibs and identical twin pairs, gains in power in the range of 10 to 30% are achieved if only one of the pair is genotyped. The theoretical results were verified by simulations. It was shown that ignoring the error in estimating the genotype of the ungenotyped relative has little impact on the estimates and on statistical power, consistent with results from quantitative trait loci (QTL) linkage studies. For genome-wide association studies in which not all relatives with phenotypes can be genotyped, our study provides a prediction of the additional power of an analysis that includes phenotypes on ungenotyped individuals, and can be used in experimental design. We show that a two-step procedure, in which missing genotypes are imputed and subsequently an association analysis is performed, is efficient and powerful.
Copyright 2005 Wiley-Liss, Inc.
Similar articles
- Powerful designs for genetic association studies that consider twins and sibling pairs with discordant genotypes.
Wessel J, Schork AJ, Tiwari HK, Schork NJ. Wessel J, et al. Genet Epidemiol. 2007 Nov;31(7):789-96. doi: 10.1002/gepi.20241. Genet Epidemiol. 2007. PMID: 17549743 - Combined linkage and association mapping of quantitative trait Loci with missing completely at random genotype data.
Fan R, Liu L, Jung J, Zhong M. Fan R, et al. Behav Genet. 2008 May;38(3):316-36. doi: 10.1007/s10519-008-9194-3. Epub 2008 Feb 27. Behav Genet. 2008. PMID: 18306033 - Bivariate association analysis for quantitative traits using generalized estimation equation.
Yang F, Tang Z, Deng H. Yang F, et al. J Genet Genomics. 2009 Dec;36(12):733-43. doi: 10.1016/S1673-8527(08)60166-6. J Genet Genomics. 2009. PMID: 20129400 - Detecting epistatic interactions contributing to quantitative traits.
Culverhouse R, Klein T, Shannon W. Culverhouse R, et al. Genet Epidemiol. 2004 Sep;27(2):141-52. doi: 10.1002/gepi.20006. Genet Epidemiol. 2004. PMID: 15305330 Review. - Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework.
Fanous AH, Kendler KS. Fanous AH, et al. Mol Psychiatry. 2005 Jan;10(1):6-13. doi: 10.1038/sj.mp.4001571. Mol Psychiatry. 2005. PMID: 15618952 Review.
Cited by
- A twin association study of nicotine dependence with markers in the CHRNA3 and CHRNA5 genes.
Maes HH, Neale MC, Chen X, Chen J, Prescott CA, Kendler KS. Maes HH, et al. Behav Genet. 2011 Sep;41(5):680-90. doi: 10.1007/s10519-011-9476-z. Epub 2011 Jul 12. Behav Genet. 2011. PMID: 21748402 Free PMC article. - Family-based association tests for genomewide association scans.
Chen WM, Abecasis GR. Chen WM, et al. Am J Hum Genet. 2007 Nov;81(5):913-26. doi: 10.1086/521580. Epub 2007 Sep 18. Am J Hum Genet. 2007. PMID: 17924335 Free PMC article. - Case-control association mapping by proxy using family history of disease.
Liu JZ, Erlich Y, Pickrell JK. Liu JZ, et al. Nat Genet. 2017 Mar;49(3):325-331. doi: 10.1038/ng.3766. Epub 2017 Jan 16. Nat Genet. 2017. PMID: 28092683 - Genotype imputation.
Li Y, Willer C, Sanna S, Abecasis G. Li Y, et al. Annu Rev Genomics Hum Genet. 2009;10:387-406. doi: 10.1146/annurev.genom.9.081307.164242. Annu Rev Genomics Hum Genet. 2009. PMID: 19715440 Free PMC article. Review. - A kernel of truth: statistical advances in polygenic variance component models for complex human pedigrees.
Blangero J, Diego VP, Dyer TD, Almeida M, Peralta J, Kent JW Jr, Williams JT, Almasy L, Göring HH. Blangero J, et al. Adv Genet. 2013;81:1-31. doi: 10.1016/B978-0-12-407677-8.00001-4. Adv Genet. 2013. PMID: 23419715 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources