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PMID: 10486333 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results.

American journal of human genetics ·Vol. 65 ·No. 4 ·1999-10-00 ·Pages 1134-47

Williams JT, Van Eerdewegh P, Almasy L, Blangero J

Abstract

We describe a variance-components method for multipoint linkage analysis that allows joint consideration of a discrete trait and a correlated continuous biological marker (e.g., a disease precursor or associated risk factor) in pedigrees of arbitrary size and complexity. The continuous trait is assumed to be multivariate normally distributed within pedigrees, and the discrete trait is modeled by a threshold process acting on an underlying multivariate normal liability distribution. The liability is allowed to be correlated with the quantitative trait, and the liability and quantitative phenotype may each include covariate effects. Bivariate discrete-continuous observations will be common, but the method easily accommodates qualitative and quantitative phenotypes that are themselves multivariate. Formal likelihood-based tests are described for coincident linkage (i.e., linkage of the traits to distinct quantitative-trait loci [QTLs] that happen to be linked) and pleiotropy (i.e., the same QTL influences both discrete-trait status and the correlated continuous phenotype). The properties of the method are demonstrated by use of simulated data from Genetic Analysis Workshop 10. In a companion paper, the method is applied to data from the Collaborative Study on the Genetics of Alcoholism, in a bivariate linkage analysis of alcoholism diagnoses and P300 amplitude of event-related brain potentials.

MeSH Terms
Chromosome Mapping/methods,statistics & numerical data Chromosomes, Human, Pair 8/genetics Chromosomes, Human, Pair 9/genetics Computer Simulation Environment Female Genetic Linkage/genetics Humans Likelihood Functions Lod Score Male Models, Genetic Multivariate Analysis Pedigree Quantitative Trait, Heritable Research Design Sample Size
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Williams J T
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. [email protected]
Van Eerdewegh P
Almasy L
Blangero J
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302570
Email
[email protected]
Published
1999-10-00
Pages
1134-47
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1288247
Subset
IM
Grants
NHLBI NIH HHS · HL45522 · United States
NIDDK NIH HHS · DK44297 · United States
NIGMS NIH HHS · R01 GM031575 · United States
NHLBI NIH HHS · P01 HL028972 · United States
NIGMS NIH HHS · F32 GM018897 · United States
NHLBI NIH HHS · P01 HL045522 · United States
NIMH NIH HHS · MH59490 · United States
NIMH NIH HHS · R01 MH059490 · United States
NIMH NIH HHS · R37 MH059490 · United States
External Links
PubMed source DOI: 10.1086/302570 PMC Full Text View journal details
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