Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1996 Apr;58(4):844–860.

A general statistical model for detecting complex-trait loci by using affected relative pairs in a genome search.

S L Smalley 1, J A Woodward 1, C G Palmer 1
PMCID: PMC1914671  PMID: 8644749

Abstract

Scanning of the human genome by use of affected relative pairs and dense sets of highly polymorphic markers or by emerging techniques such as genomic mismatch scanning. (GMS) is making it possible to identify the genetic etiology of a disease through detection of susceptibility loci. We present a general statistical model and test to detect disease genes, using affected relative pairs and either markers or GMS technologies in a genome search. There are an exact test and large-sample normal approximation that control for the elevated probability of false detection of linkage in a genome search. The approach can be used to determine the sample size needed to obtain a prespecified power to detect a disease gene in the presence of etiologic heterogeneity for a single class or mixture of relative classes, with any number of markers, or clones, markers PIC values, or mapping function. The approach is used to examine differences in performance of markers and GMS technologies in a common statistical framework and to provide practical information for designing studies of complex traits.

Full text

PDF
844

Selected References

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

  1. Babron M. C., Martinez M., Bonaïti-Pellié C., Clerget-Darpoux F. Linkage detection by the Affected-Pedigree-Member method: what is really tested? Genet Epidemiol. 1993;10(6):389–394. doi: 10.1002/gepi.1370100610. [DOI] [PubMed] [Google Scholar]
  2. Bishop D. T., Williamson J. A. The power of identity-by-state methods for linkage analysis. Am J Hum Genet. 1990 Feb;46(2):254–265. [PMC free article] [PubMed] [Google Scholar]
  3. Blackwelder W. C., Elston R. C. A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol. 1985;2(1):85–97. doi: 10.1002/gepi.1370020109. [DOI] [PubMed] [Google Scholar]
  4. Brown D. L., Gorin M. B., Weeks D. E. Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis. Am J Hum Genet. 1994 Mar;54(3):544–552. [PMC free article] [PubMed] [Google Scholar]
  5. Feingold E., Brown P. O., Siegmund D. Gaussian models for genetic linkage analysis using complete high-resolution maps of identity by descent. Am J Hum Genet. 1993 Jul;53(1):234–251. [PMC free article] [PubMed] [Google Scholar]
  6. Green J. R., Woodrow J. C. Sibling Method for Detecting HLA-linked genes in disease. Tissue Antigens. 1977 Jan;9(1):31–35. doi: 10.1111/j.1399-0039.1977.tb01076.x. [DOI] [PubMed] [Google Scholar]
  7. Hodge S. E. Some epistatic two-locus models of disease. I. Relative risks and identity-by-descent distributions in affected sib pairs. Am J Hum Genet. 1981 May;33(3):381–395. [PMC free article] [PubMed] [Google Scholar]
  8. Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
  9. Lange K. The affected sib-pair method using identity by state relations. Am J Hum Genet. 1986 Jul;39(1):148–150. [PMC free article] [PubMed] [Google Scholar]
  10. Nelson S. F., McCusker J. H., Sander M. A., Kee Y., Modrich P., Brown P. O. Genomic mismatch scanning: a new approach to genetic linkage mapping. Nat Genet. 1993 May;4(1):11–18. doi: 10.1038/ng0593-11. [DOI] [PubMed] [Google Scholar]
  11. Olson J. M. Multipoint linkage analysis using sib pairs: an interval mapping approach for dichotomous outcomes. Am J Hum Genet. 1995 Mar;56(3):788–798. [PMC free article] [PubMed] [Google Scholar]
  12. Renwick J. H. Progress in mapping human autosomes. Br Med Bull. 1969 Jan;25(1):65–73. doi: 10.1093/oxfordjournals.bmb.a070673. [DOI] [PubMed] [Google Scholar]
  13. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990 Feb;46(2):222–228. [PMC free article] [PubMed] [Google Scholar]
  14. Suarez B. K. The affected sib pair IBD distribution for HLA-linked disease susceptibility genes. Tissue Antigens. 1978 Aug;12(2):87–93. doi: 10.1111/j.1399-0039.1978.tb01303.x. [DOI] [PubMed] [Google Scholar]
  15. Thomson G., Motro U. Affected sib pair identity by state analyses. Genet Epidemiol. 1994;11(4):353–364. doi: 10.1002/gepi.1370110405. [DOI] [PubMed] [Google Scholar]

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

RESOURCES