title: Linkage analysis of alcohol dependence using both affected and discordant sib pairs.
abstract: The basic idea of affected-sib-pair (ASP) linkage analysis is to test whether the inheritance pattern of a marker deviates from Mendelian expectation in a sample of ASPs. The test depends on an assumed Mendelian control distribution of the number of marker alleles shared identical by descent (IBD), i.e., 1/4, 1/2, and 1/4 for 2, 1, and 0 allele(s) IBD, respectively. However, Mendelian transmission may not always hold, for example because of inbreeding or meiotic drive at the marker or a nearby locus. A more robust and valid approach is to incorporate discordant-sib-pairs (DSPs) as controls to avoid possible false-positive results. To be robust to deviation from Mendelian transmission, here we analyzed Collaborative Study on the Genetics of Alcoholism data by modifying the ASP LOD score method to contrast the estimated distribution of the number of allele(s) shared IBD by ASPs with that by DSPs, instead of with the expected distribution under the Mendelian assumption. This strategy assesses the difference in IBD sharing between ASPs and the IBD sharing between DSPs. Further, it works better than the conventional LOD score ASP linkage method in these data in the sense of avoiding false-positive linkage evidence.
authors.affiliation: Department of Epidemiology & Biostatistics, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building, Cleveland, OH 44106, USA. shih@darwin.epbi.cwru.edu
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Shih
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Xing
authors.forename: Moumita
authors.initials: M
authors.lastname: Sinha
authors.forename: Yeunjoo
authors.initials: Y
authors.lastname: Song
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D035781:Siblings; D012984:Software
chemical_list: D005819:Genetic Markers