Multivariate and multilocus variance components method, based on structural relationships to assess quantitative trait linkage via SEGPATH

Michael A. Province, T. K. Rice, I. B. Borecki, C. Gu, A. Kraja, D. C. Rao

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

A general-purpose modeling framework for performing path and segregation analysis jointly, called SEGPATH (Province and Rao [1995] Stat. Med. 7:185-198), has been extended to cover "model-free" robust, variance-components linkage analysis, based on identity-by-descent (IBD) sharing. These extended models can be used to analyze linkage to a single marker or to perform multipoint linkage analysis, with a single phenotype or multivariate vector of phenotypes, in pedigrees. Within a single, consistent approach, SEGPATH models can perform segregation analysis, path analysis, linkage analysis, or combinations thereof. SEGPATH models can incorporate environmental or other measured covariate fixed effects (including measured genotypes), genotype-specific covariate effects, population heterogeneity models, repeatedmeasures models, longitudinal models, autoregressive models, developmental models, gene-by-environment interaction models, etc., with or without linkage components. The data analyzed can have any missing value structure (assumed missing at random), with entire individuals missing, or missing on one or more measurements. Corrections for ascertainment can be made on a vector of phenotypes and/or other measures. Because of the flexibility of the class of models, the SEGPATH approach can also be used in nongenetic applications where there is a hierarchical structure, such as longitudinal, repeated-measures, time series, or nested models. A variety of specific models are provided, as well as some comparisons with other linkage analysis models. Particular applications demonstrate the importance of correctly accounting for the extraneous sources of familial resemblance, as can be done easily with these SEGPATH models, so as to give added power to detect linkage as well as to protect against spuriously inferring linkage.

Original languageEnglish
Pages (from-to)128-138
Number of pages11
JournalGenetic Epidemiology
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Maximum likelihood
  • Path analysis
  • Quantitative trait linkage
  • Variance components

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