https://scholars.lib.ntu.edu.tw/handle/123456789/508131
標題: | Multinomial logistic regression approach to haplotype association analysis in population-based case-control studies | 作者: | Chen Y.-H. JAU-TSUEN KAO |
公開日期: | 2006 | 卷: | 7 | 起(迄)頁: | 43 | 來源出版物: | BMC Genetics | 摘要: | Background: The genetic association analysis using haplotypes as basic genetic units is anticipated to be a powerful strategy towards the discovery of genes predisposing human complex diseases. In particular, the increasing availability of high-resolution genetic markers such as the single-nucleotide polymorphisms (SNPs) has made haplotype-based association analysis an attractive alternative to single marker analysis. Results: We consider haplotype association analysis under the population-based case-control study design. A multinomial logistic model is proposed for haplotype analysis with unphased genotype data, which can be decomposed into a prospective logistic model for disease risk as well as a model for the haplotype-pair distribution in the control population. Environmental factors can be readily incorporated and hence the haplotype-environment interaction can be assessed in the proposed model. The maximum likelihood estimation with unphased genotype data can be conveniently implemented in the proposed model by applying the EM algorithm to a prospective multinomial logistic regression model and ignoring the case-control design. We apply the proposed method to the hypertriglyceridemia study and identifies 3 haplotypes in the apolipoprotein A5 gene that are associated with increased risk for hypertriglyceridemia. A haplotype-age interaction effect is also identified. Simulation studies show that the proposed estimator has satisfactory finite-sample performances. Conclusion: Our results suggest that the proposed method can serve as a useful alternative to existing methods and a reliable tool for the case-control haplotype-based association analysis. ? 2006 Chen and Kao; licensee BioMed Central Ltd. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/508131 | ISSN: | 1471-2156 | DOI: | 10.1186/1471-2156-7-43 | SDG/關鍵字: | apolipoprotein A5; algorithm; article; case control study; controlled study; disease association; disease simulation; environmental factor; female; genetic association; genetic predisposition; genetic risk; genotype; genotype environment interaction; haplotype; high risk patient; human; hypertriglyceridemia; major clinical study; male; mathematical computing; maximum likelihood method; multinomial logistic regression analysis; population research; regression analysis; reliability; risk assessment; single nucleotide polymorphism; Algorithms; Apolipoproteins; Apolipoproteins A; Case-Control Studies; Female; Genetic Markers; Haplotypes; Humans; Hypertriglyceridemia; Logistic Models; Male; Models, Genetic; Polymorphism, Single Nucleotide |
顯示於: | 醫學檢驗暨生物技術學系 |
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