Title :
Fine-Scale Genetic Mapping Using Independent Component Analysis
Author :
Dawy, Zaher ; Sarkis, Michel ; Hagenauer, Joachim ; Mueller, Jakob C.
Author_Institution :
Dept. of Electr. & Comput. Eng., American Univ. of Beirut, Beirut
Abstract :
The aim of genetic mapping is to locate the loci responsible for specific traits such as complex diseases. These traits are normally caused by mutations at multiple loci of unknown locations and interactions. In this work, we model the biological system that relates DNA polymorphisms with complex traits as a linear mixing process. Given this model, we propose a new fine-scale genetic mapping method based on independent component analysis. The proposed method outputs both independent associated groups of SNPs in addition to specific associated SNPs with the phenotype. It is applied to a clinical data set for the Schizophrenia disease with 368 individuals and 42 SNPs. It is also applied to a simulation study to investigate in more depth its performance. The obtained results demonstrate the novel characteristics of the proposed method compared to other genetic mapping methods. Finally, we study the robustness of the proposed method with missing genotype values and limited sample sizes.
Keywords :
DNA; diseases; genetics; independent component analysis; molecular biophysics; molecular configurations; polymorphism; DNA polymorphisms; Schizophrenia disease; association mapping; biomolecule interactions; fine-scale genetic mapping; independent component analysis; linear mixing process; linkage disequilibrium; mutations; single nucleotide polymorphisms; Independent component analysis (ICA); association mapping; complex diseases; linkage disequilibrium; principal component analysis (PCA); single nucleotide polymorphisms (SNPs); Algorithms; Chromosome Mapping; Data Interpretation, Statistical; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Models, Genetic; Models, Statistical; Polymorphism, Single Nucleotide; Principal Component Analysis; Schizophrenia; Sensitivity and Specificity; Sequence Analysis, DNA;
Journal_Title :
Computational Biology and Bioinformatics, IEEE/ACM Transactions on
DOI :
10.1109/TCBB.2007.1072