title: Association tests in nuclear families.
abstract: We present a conditional likelihood approach for testing linkage disequilibrium in nuclear families having multiple affected offspring. The likelihood, conditioned on the identity-by-descent (IBD) structure of the sibling genotypes, is unaffected by familial correlation in disease status that arises from linkage between a marker locus and the unobserved trait locus. Two such conditional likelihoods are compared: one that conditions on IBD and phase of the transmitted alleles and a second which conditions only on IBD of the transmitted alleles. Under the log-additive model, the first likelihood is equivalent to the allele-counting methods proposed in the literature. The second likelihood is valid under the added assumption of equal male and female recombination fractions. In a simulation study, we demonstrated that in sibships having two or three affected siblings the score test from each likelihood had the correct test size for testing disequilibrium. They also led to equivalent power to detect linkage disequilibrium at the 5% significance level.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, Calif 9089-9011, USA. kims@usc.edu
authors.forename: K D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: W J
authors.initials: WJ
authors.lastname: Gauderman
mesh_terms: D003198:Computer Simulation; D005192:Family Health; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008957:Models, Genetic
chemical_list: D005819:Genetic Markers