LINKAGE STRATEGIES FOR GENETICALLY COMPLEX TRAITS .2. THE POWER OF AFFECTED RELATIVE PAIRS

  • 1 February 1990
    • journal article
    • research article
    • Vol. 46  (2) , 229-241
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 large .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.