Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 Jan;64(1):259–267. doi: 10.1086/302193

Combined linkage and association sib-pair analysis for quantitative traits.

D W Fulker 1, S S Cherny 1, P C Sham 1, J K Hewitt 1
PMCID: PMC1377724  PMID: 9915965

Abstract

An extension to current maximum-likelihood variance-components procedures for mapping quantitative-trait loci in sib pairs that allows a simultaneous test of allelic association is proposed. The method involves modeling of the allelic means for a test of association, with simultaneous modeling of the sib-pair covariance structure for a test of linkage. By partitioning of the mean effect of a locus into between- and within-sibship components, the method controls for spurious associations due to population stratification and admixture. The power and efficacy of the method are illustrated through simulation of various models of both real and spurious association.

Full Text

The Full Text of this article is available as a PDF (221.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison D. B. Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet. 1997 Mar;60(3):676–690. [PMC free article] [PubMed] [Google Scholar]
  2. Almasy L., Blangero J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet. 1998 May;62(5):1198–1211. doi: 10.1086/301844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amos C. I. Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet. 1994 Mar;54(3):535–543. [PMC free article] [PubMed] [Google Scholar]
  4. Boehnke M., Langefeld C. D. Genetic association mapping based on discordant sib pairs: the discordant-alleles test. Am J Hum Genet. 1998 Apr;62(4):950–961. doi: 10.1086/301787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Curtis D., Sham P. C. A note on the application of the transmission disequilibrium test when a parent is missing. Am J Hum Genet. 1995 Mar;56(3):811–812. [PMC free article] [PubMed] [Google Scholar]
  6. Curtis D. Use of siblings as controls in case-control association studies. Ann Hum Genet. 1997 Jul;61(Pt 4):319–333. doi: 10.1046/j.1469-1809.1998.6210089.x. [DOI] [PubMed] [Google Scholar]
  7. Fulker D. W., Cherny S. S. An improved multipoint sib-pair analysis of quantitative traits. Behav Genet. 1996 Sep;26(5):527–532. doi: 10.1007/BF02359758. [DOI] [PubMed] [Google Scholar]
  8. Haseman J. K., Elston R. C. The investigation of linkage between a quantitative trait and a marker locus. Behav Genet. 1972 Mar;2(1):3–19. doi: 10.1007/BF01066731. [DOI] [PubMed] [Google Scholar]
  9. Kruglyak L., Lander E. S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet. 1995 Aug;57(2):439–454. [PMC free article] [PubMed] [Google Scholar]
  10. Lazzeroni L. C., Lange K. A conditional inference framework for extending the transmission/disequilibrium test. Hum Hered. 1998 Mar-Apr;48(2):67–81. doi: 10.1159/000022784. [DOI] [PubMed] [Google Scholar]
  11. Rabinowitz D. A transmission disequilibrium test for quantitative trait loci. Hum Hered. 1997 Nov-Dec;47(6):342–350. doi: 10.1159/000154433. [DOI] [PubMed] [Google Scholar]
  12. Sham P. C., Curtis D. Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet. 1995 Jan;59(Pt 1):97–105. doi: 10.1111/j.1469-1809.1995.tb01608.x. [DOI] [PubMed] [Google Scholar]
  13. Sham P. Transmission/disequilibrium tests for multiallelic loci. Am J Hum Genet. 1997 Sep;61(3):774–778. doi: 10.1016/S0002-9297(07)64343-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Spielman R. S., Ewens W. J. A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet. 1998 Feb;62(2):450–458. doi: 10.1086/301714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Spielman R. S., McGinnis R. E., Ewens W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed] [Google Scholar]
  16. Terwilliger J. D., Ott J. A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. Hum Hered. 1992;42(6):337–346. doi: 10.1159/000154096. [DOI] [PubMed] [Google Scholar]
  17. Xu S., Atchley W. R. A random model approach to interval mapping of quantitative trait loci. Genetics. 1995 Nov;141(3):1189–1197. doi: 10.1093/genetics/141.3.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES