title: An expectation-maximization-likelihood-ratio test for handling missing data: application in experimental crosses.
abstract: The mapping of quantitative trait loci (QTL) is an important research question in animal and human studies. Missing data are common in such study settings, and ignoring such missing data may result in biased estimates of the genotypic effect and thus may eventually lead to errant results and incorrect inferences. In this article, we developed an expectation-maximization (EM)-likelihood-ratio test (LRT) in QTL mapping. Simulation studies based on two different types of phylogenetic models revealed that the EM-LRT, a statistical technique that uses EM-based parameter estimates in the presence of missing data, offers a greater statistical power compared with the ordinary analysis-of-variance (ANOVA)-based test, which discards incomplete data. We applied both the EM-LRT and the ANOVA-based test in a real data set collected from F2 intercross studies of inbred mouse strains. It was found that the EM-LRT makes an optimal use of the observed data and its advantages over the ANOVA F-test are more pronounced when more missing data are present. The EM-LRT method may have important implications in QTL mapping in experimental crosses.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. tniu@rics.bwh.harvard.edu
authors.forename: Tianhua
authors.initials: T
authors.lastname: Niu
authors.forename: Adam A
authors.initials: AA
authors.lastname: Ding
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Klaus
authors.initials: K
authors.lastname: Lindpaintner
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology*; D002874:Chromosome Mapping; D003198:Computer Simulation; D003433:Crosses, Genetic; D008040:Genetic Linkage; D005819:Genetic Markers; D016013:Likelihood Functions; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D015233:Models, Statistical; D009929:Organ Size; D010802:Phylogeny; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers
references.citation: Genetics. 2000 Sep;156(1):457-67
references.pmid: 10978308
references.citation: Curr Hypertens Rep. 1999 Feb-Mar;1(1):25-30
references.pmid: 10981039
references.citation: Genetics. 2001 Sep;159(1):371-87
references.pmid: 11560912
references.citation: Theor Appl Genet. 2003 Feb;106(4):759-64
references.pmid: 12596007
references.citation: Genetics. 1998 Jan;148(1):349-60
references.pmid: 9475745
references.citation: Physiol Genomics. 2003 Aug 15;14(3):209-16
references.pmid: 12799471
references.citation: Am J Hum Genet. 1988 Jan;42(1):113-24
references.pmid: 2892394
references.citation: Genetics. 1989 Jan;121(1):185-99
references.pmid: 2563713
references.citation: Nat Genet. 1996 Aug;13(4):429-34
references.pmid: 8696337
references.citation: BMC Neurosci. 2001;2:5
references.pmid: 11319941