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

Jeff T. Williams, Paul Van Eerdewegh, Laura Almasy, John Blangero

Research output: Contribution to journalArticle

185 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1134-1147
Number of pages14
JournalAmerican Journal of Human Genetics
Volume65
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

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Multivariate Analysis
Joints
Quantitative Trait Loci
Pedigree
Phenotype
Alcoholism
Normal Distribution
Evoked Potentials
Biomarkers
Education
Brain

ASJC Scopus subject areas

  • Genetics

Cite this

Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results. / Williams, Jeff T.; Van Eerdewegh, Paul; Almasy, Laura; Blangero, John.

In: American Journal of Human Genetics, Vol. 65, No. 4, 1999, p. 1134-1147.

Research output: Contribution to journalArticle

Williams, Jeff T. ; Van Eerdewegh, Paul ; Almasy, Laura ; Blangero, John. / Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results. In: American Journal of Human Genetics. 1999 ; Vol. 65, No. 4. pp. 1134-1147.
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