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Family-based association analysis with ordered categorical phenotypes, covariates and interactions

Baksh, MF; Balding, DJ; Vyse, TJ; Whittaker, JC; (2007) Family-based association analysis with ordered categorical phenotypes, covariates and interactions. GENET EPIDEMIOL , 31 (1) 1 - 8. 10.1002/gepi.20183.

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Abstract

Genetic association analyses of family-based studies with ordered categorical phenotypes are often conducted using methods either for quantitative or for binary traits, which can lead to suboptimal analyses. Here we present an alternative likelihood-based method of analysis for single nucleotide polymorphism (SNP) genotypes and ordered categorical phenotypes in nuclear families of any size. Our approach, which extends our previous work for binary phenotypes, permits straightforward inclusion of covariate, gene-gene and gene-covariate interaction terms in the likelihood, incorporates a simple model for ascertainment and allows for family-specific effects in the hypothesis test. Additionally, our method produces interpretable parameter estimates and valid confidence intervals. We assess the proposed method using simulated data, and apply it to a polymorphism in the c-reactive protein (CRP) gene typed in families collected to investigate human systemic lupus erythematosus. By including sex interactions in the analysis, we show that the polymorphism is associated with anti-nuclear autoantibody (ANA) production in females, while there appears to be no effect in males.

Type: Article
Title: Family-based association analysis with ordered categorical phenotypes, covariates and interactions
DOI: 10.1002/gepi.20183
Keywords: continuation ratio, gene-environment interaction, ordinal trait, proportional odds, NUCLEAR FAMILIES, ORDINAL TRAITS, LINKAGE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/100498
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