Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data

Cengizhan Acikel,1 Yesim Aydin Son,2 Cemil Celik,3 Husamettin Gul4 1Department of Biostatistics, Gulhane Military Medical Academy, 2Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, 3Department of Medical Psychiatry, 4Department of Medical Informati...

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Autores principales:	Acikel C, Aydin Son Y, Celik C, Gul H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	GWAS Bipolar disorders SNP DOCK10 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/252f60f8aa564dbbb02c00df6128210f
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spelling	oai:doaj.org-article:252f60f8aa564dbbb02c00df6128210f2021-12-02T01:11:52ZEvaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data1178-2021https://doaj.org/article/252f60f8aa564dbbb02c00df6128210f2016-11-01T00:00:00Zhttps://www.dovepress.com/evaluation-of-novel-candidate-variations-and-their-interactions-relate-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Cengizhan Acikel,1 Yesim Aydin Son,2 Cemil Celik,3 Husamettin Gul4 1Department of Biostatistics, Gulhane Military Medical Academy, 2Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, 3Department of Medical Psychiatry, 4Department of Medical Informatics, Gulhane Military Medical Academy, Ankara, Turkey Background: Multifactor dimensionality reduction (MDR) is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs). The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. Methods: This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1) data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor) were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity), precision (positive predictive value), and F-measure. Results: Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Conclusion: Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and diagnostic tests. Nevertheless, we need to emphasize that translation of genomic models to the clinical setting requires models with higher classification performance. Keywords: Bipolar disorders, GWAS, MDR, Data Mining, SNP, Decision SupportAcikel CAydin Son YCelik CGul HDove Medical PressarticleGWASBipolar disordersSNPDOCK10Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 12, Pp 2997-3004 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	GWAS Bipolar disorders SNP DOCK10 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	GWAS Bipolar disorders SNP DOCK10 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Acikel C Aydin Son Y Celik C Gul H Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
description	Cengizhan Acikel,1 Yesim Aydin Son,2 Cemil Celik,3 Husamettin Gul4 1Department of Biostatistics, Gulhane Military Medical Academy, 2Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, 3Department of Medical Psychiatry, 4Department of Medical Informatics, Gulhane Military Medical Academy, Ankara, Turkey Background: Multifactor dimensionality reduction (MDR) is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs). The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. Methods: This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1) data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor) were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity), precision (positive predictive value), and F-measure. Results: Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Conclusion: Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and diagnostic tests. Nevertheless, we need to emphasize that translation of genomic models to the clinical setting requires models with higher classification performance. Keywords: Bipolar disorders, GWAS, MDR, Data Mining, SNP, Decision Support
format	article
author	Acikel C Aydin Son Y Celik C Gul H
author_facet	Acikel C Aydin Son Y Celik C Gul H
author_sort	Acikel C
title	Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
title_short	Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
title_full	Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
title_fullStr	Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
title_full_unstemmed	Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data
title_sort	evaluation of novel candidate variations and their interactions related to bipolar disorders: analysis of gwas data
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/252f60f8aa564dbbb02c00df6128210f
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Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data

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