Exploiting gene × gene interaction in linkage analysis

Yungui Huang; Christopher W Bartlett; Alberto M Segre; Jeffrey R O'Connell; LaVonne Mangin; Veronica J Vieland

doi:10.1186/1753-6561-1-S1-S64

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Exploiting gene × gene interaction in linkage analysis

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Exploiting gene × gene interaction in linkage analysis

Yungui Huang, Christopher W Bartlett, Alberto M Segre, Jeffrey R O'Connell, LaVonne Mangin and Veronica J Vieland

BMC proceedings, Vol.1(Suppl 1), pp.S64-S64

12/18/2007

DOI: 10.1186/1753-6561-1-S1-S64

PMCID: PMC2367485

PMID: 18466565

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Abstract

When two genes interact to cause a clinically important phenotype, it would seem reasonable to expect that we could leverage genotypic information at one of the loci in order to improve our ability to detect the other. We were therefore interested in extending the posterior probability of linkage (PPL), a class of linkage statistics we have been developing over the past decade, in order to explicitly allow for gene × gene interaction. In this report we utilize a new implementation of the PPL incorporating liability classes (LCs), which provide a direct parameterization of gene × gene interaction by allowing the penetrances at the locus being evaluated to depend upon measured genotypes at a known locus. With knowledge of the generating model for the simulated rheumatoid arthritis (RA) data, we selected two loci for examination: Locus A, which in interaction with the HLA-DR antigen locus affects risk of the dichotomous RA phenotype; and Locus E, which in interaction with DR affects quantitative levels of the anti-CCP phenotype. The data comprised nuclear families of two parents and an affected sib pair (ASP). Our results confirm theoretical work suggesting that gene × gene interactions CANNOT be leveraged to improve linkage detection for dichotomous traits based on affecteds-only data structures. However, incorporation of DR-based LCs did lead to appreciably higher quantitative trait PPLs. This suggests that gene × gene interactions could be effectively used in quantitative trait analyses even when families have been ascertained as ASPs for a related dichotomous trait.

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Title: Subtitle: Exploiting gene × gene interaction in linkage analysis
Creators: Yungui Huang - Nationwide Children's Hospital
Christopher W Bartlett - University of Iowa
Alberto M Segre - University of Iowa
Jeffrey R O'Connell - University of Maryland Medical Center
LaVonne Mangin - Nationwide Children's Hospital
Veronica J Vieland - The Ohio State University
Resource Type: Abstract
Publication Details: BMC proceedings, Vol.1(Suppl 1), pp.S64-S64
DOI: 10.1186/1753-6561-1-S1-S64
PMID: 18466565
PMCID: PMC2367485
NLM abbreviation: BMC Proc
ISSN: 1753-6561
eISSN: 1753-6561
Publisher: BioMed Central
Language: English
Date published: 12/18/2007
Academic Unit: Nursing; Fraternal Order of Eagles Diabetes Research Center; Computer Science
Record Identifier: 9984370854002771

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