Different models and single-nucleotide polymorphisms signal the simulated weak gene-gene interaction for a quantitative trait using haplotype-based and mixed models testingReport as inadecuate




Different models and single-nucleotide polymorphisms signal the simulated weak gene-gene interaction for a quantitative trait using haplotype-based and mixed models testing - Download this document for free, or read online. Document in PDF available to download.

BMC Proceedings

, 3:S77

First Online: 15 December 2009DOI: 10.1186-1753-6561-3-S7-S77

Cite this article as: Kovac, I.P. & Dubé, MP. BMC Proc 2009 3Suppl 7: S77. doi:10.1186-1753-6561-3-S7-S77

Abstract

Knowledge of simulated genetic effects facilitates interpretation of methodological studies. Genetic interactions for common disorders are likely numerous and weak. Using the 200 replicates of the Genetic Analysis Workshop 16 GAW16 Problem 3 simulated data, we compared the statistical power to detect weak gene-gene interactions using a haplotype-based test in the UNPHASED software with genotypic mixed model GMM and additive mixed model AMM mixed linear regression model in SAS. We assumed a candidate-gene approach where a single-nucleotide polymorphism SNP in one gene is fixed and multiple SNPs are at the second gene. We analyzed the quantitative low-density lipoprotein trait heritability 0.7%, modulated by simulated interaction of rs4648068 from 4q24 and another gene on 8p22, where we analyzed seven SNPs. We generally observed low power calculated per SNP ≤ 37% at the 0.05 level, with the haplotype-based test being inferior. Over all tests, the haplotype-based test performed within chance, while GMM and AMM had low power ~10%. The haplotype-based and mixed models detected signals at different SNPs. The haplotype-based test detected a signal in 50 unique replicates; GMM and AMM featured both shared and distinct SNPs and replicates 65 replicates shared, 41 GMM, 27 AMM. Overall, the statistical signal for the weak gene-gene interaction appears sensitive to the sample structure of the replicates. We conclude that using more than one statistical approach may increase power to detect such signals in studies with limited number of loci such as replications. There were no results significant at the conservative 10 genome-wide level.

List of abbreviations usedAMMAdditive mixed model

GAW16Genetic Analysis Workshop 16

GMMGenotypic mixed model

HDLHigh-density lipoprotein

LDLLow-density lipoprotein

LPLLipoprotein lipase precursor

SNPSingle-nucleotide polymorphism

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Author: Ilija P Kovac - Marie-Pierre Dubé

Source: https://link.springer.com/



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