Linkage strategies for genetically complex traits. II. The power of affected relative pairs - PubMed (original) (raw)

Linkage strategies for genetically complex traits. II. The power of affected relative pairs

N Risch. Am J Hum Genet. 1990 Feb.

Abstract

The power to detect disease-susceptibility loci through linkage analysis using pairs of affected relatives and affected-unaffected pairs is examined. Allelic identity by descent (ibd) for a completely polymorphic marker for sibling, uncle-nephew, grandparent-grandchild, half-sib, and first-cousin pairs is considered. Affected-unaffected pairs generally represent a poor strategy. For single-locus models, ibd depends on lambda R, the risk ratio for type R relatives compared with population prevalence, and the recombination fraction theta. The ibd for grandparent-grandchild pairs is least affected by recombination, followed by sibs, half-sib, uncle-nephew, and first-cousin pairs. For diseases with large lambda values and for small theta values, distant relatives offer greater power. For larger theta values, grandparent-grandchild pairs are best; for small lambda values, sibs are best. Additive and multiplicative multilocus models are considered. For the multiplicative model, the same formulas as in the single-locus model apply, except that lambda iR (for the ith contributing locus) is substituted for lambda R. For the additive model, the deviation from null expectation for ibd is divided among all contributing loci. Compared with the multiplicative model, for an additive model there is usually greater advantage in distant relationships. Multipoint analysis using linked marker loci for affected relative pairs is described. Simultaneous use of multiple markers diminishes the effect of recombination and allows for localization of the disease-susceptibility locus.

PubMed Disclaimer

Comment in

Similar articles

Cited by

References

    1. Proc Natl Acad Sci U S A. 1988 Jan;85(1):1-5 - PubMed
    1. Genet Epidemiol. 1988;5(3):151-69 - PubMed
    1. Am J Hum Genet. 1990 Feb;46(2):254-65 - PubMed
    1. Ann Hum Genet. 1978 Jul;42(1):87-94 - PubMed
    1. Ann Hum Genet. 1971 Oct;35(2):225-36 - PubMed

Publication types

MeSH terms

LinkOut - more resources