title: Haseman-Elston weighted by marker informativity.
abstract: In the Haseman-Elston approach the squared phenotypic difference is regressed on the proportion of alleles shared identical by descent (IBD) to map a quantitative trait to a genetic marker. In applications the IBD distribution is estimated and usually cannot be determined uniquely owing to incomplete marker information. At Genetic Analysis Workshop (GAW) 13, Jacobs et al. [BMC Genet 2003, 4(Suppl 1):S82] proposed to improve the power of the Haseman-Elston algorithm by weighting for information available from marker genotypes. The authors did not show, however, the validity of the employed asymptotic distribution. In this paper, we use the simulated data provided for GAW 14 and show that weighting Haseman-Elston by marker information results in increased type I error rates. Specifically, we demonstrate that the number of significant findings throughout the chromosome is significantly increased with weighting schemes. Furthermore, we show that the classical Haseman-Elston method keeps its nominal significance level when applied to the same data. We therefore recommend to use Haseman-Elston with marker informativity weights only in conjunction with empirical p-values. Whether this approach in fact yields an increase in power needs to be investigated further.
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Ratzeburger Allee 160, Haus 4, 23538 Lübeck, Germany. daniel.franke@imbs.uni-luebeck.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Franke
authors.forename: André
authors.initials: A
authors.lastname: Kleensang
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003198:Computer Simulation; D030541:Databases, Genetic; D005006:Ethnicity / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008957:Models, Genetic; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers