title: SHARE: an adaptive algorithm to select the most informative set of SNPs for candidate genetic association.
abstract: Association studies have been widely used to identify genetic liability variants for complex diseases. While scanning the chromosomal region 1 single nucleotide polymorphism (SNP) at a time may not fully explore linkage disequilibrium, haplotype analyses tend to require a fairly large number of parameters, thus potentially losing power. Clustering algorithms, such as the cladistic approach, have been proposed to reduce the dimensionality, yet they have important limitations. We propose a SNP-Haplotype Adaptive REgression (SHARE) algorithm that seeks the most informative set of SNPs for genetic association in a targeted candidate region by growing and shrinking haplotypes with 1 more or less SNP in a stepwise fashion, and comparing prediction errors of different models via cross-validation. Depending on the evolutionary history of the disease mutations and the markers, this set may contain a single SNP or several SNPs that lay a foundation for haplotype analyses. Haplotype phase ambiguity is effectively accounted for by treating haplotype reconstruction as a part of the learning procedure. Simulations and a data application show that our method has improved power over existing methodologies and that the results are informative in the search for disease-causal loci.
authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M2-C200, Seattle, WA 98109, USA. jdai@fhcrc.org
authors: James Y
authors: JY
authors: Dai
authors: Michael
authors: M
authors: Leblanc
authors: Nicholas L
authors: NL
authors: Smith
authors: Bruce
authors: B
authors: Psaty
authors: Charles
authors: C
authors: Kooperberg
mesh_terms: D000368:Aged; D000465:Algorithms; D056808:Biostatistics / Q000379:methods; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008074:Lipoproteins / Q000235:genetics; D008875:Middle Aged; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D020246:Venous Thrombosis / Q000235:genetics
chemical_list: D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor