Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
9915966
TITLE
A simulation study of the effects of assignment of prior identity-by-descent probabilities to unselected sib pairs, in covariance-structure modeling of a quantitative-trait locus.
ABSTRACT
Sib pair-selection strategies, designed to identify the most informative sib pairs in order to detect a quantitative-trait locus (QTL), give rise to a missing-data problem in genetic covariance-structure modeling of QTL effects. After selection, phenotypic data are available for all sibs, but marker data-and, consequently, the identity-by-descent (IBD) probabilities-are available only in selected sib pairs. One possible solution to this missing-data problem is to assign prior IBD probabilities (i.e., expected values) to the unselected sib pairs. The effect of this assignment in genetic covariance-structure modeling is investigated in the present paper. Two maximum-likelihood approaches to estimation are considered, the pi-hat approach and the IBD-mixture approach. In the simulations, sample size, selection criteria, QTL-increaser allele frequency, and gene action are manipulated. The results indicate that the assignment of prior IBD probabilities results in serious estimation bias in the pi-hat approach. Bias is also present in the IBD-mixture approach, although here the bias is generally much smaller. The null distribution of the log-likelihood ratio (i.e., in absence of any QTL effect) does not follow the expected null distribution in the pi-hat approach after selection. In the IBD-mixture approach, the null distribution does agree with expectation.
DATE PUBLISHED
1999 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 1999/01/23 19:27
medline 2000/03/21 09:00
entrez 1999/01/23 19:27
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Dolan CV Dolan C V CV Psychology Faculty, University of Amsterdam, The Netherlands. op_dolan@macmail.psy.uva.nl
Boomsma DI Boomsma D I DI
Neale MC Neale M C MC
INVESTIGATORS
JOURNAL
VOLUME: 64
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 1999
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alleles
Gene Frequency
Genetic Markers
Humans
Models, Genetic
Nuclear Family
Quantitative Trait, Heritable
Software
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
OTHER ID's