title: Increasing power by using haplotype similarity in a multimarker transmission/disequilibrium test.
abstract: It is already known that power in multimarker transmission/disequilibrium tests may improve with the number of markers as some associations may require several markers to be captured. However, a mechanism such as haplotype grouping must be used to avoid incremental complexity with the number of markers. 2G, a state-of-the-art transmission/disequilibrium test, implements this mechanism to its maximum extent by grouping haplotypes into only two groups, high and low-risk haplotypes, so that the test has only one degree of freedom regardless of the number of markers. The test checks whether those haplotypes more often transmitted from parents to offspring are truly high-risk haplotypes. In this paper we use haplotype similarity as prior knowledge to classify haplotypes as high or low risk ones and start with those haplotypes in which the prior will have lower impact i.e. those with the largest differences between transmission and non-transmission counts. If their counts are very different, the prior knowledge has little effect and haplotypes are classified as low or high risk as 2G does. We show a substantial gain in power achieved by this approach, in both simulation and real data sets.
authors.affiliation: Department of Computer Languages and Systems-CITIC, Universidad de Granada, Granada 18071, Spain. mabad@ugr.es
authors.forename: María M
authors.initials: MM
authors.lastname: Abad-Grau
authors.forename: Nuria
authors.initials: N
authors.lastname: Medina-Medina
authors.forename: Serafín
authors.initials: S
authors.lastname: Moral
authors.forename: Rosana
authors.initials: R
authors.lastname: Montes-Soldado
authors.forename: Sergio
authors.initials: S
authors.lastname: Torres-Sánchez
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D019295:Computational Biology; D003198:Computer Simulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers