How to Select Tag SNPs in Genetic Association Studies? The CLONTagger Method with Parameter Optimization

Abstract

Selection of genetic variants is a crucial first step in the rational design of studies aimed at explaining individual differences in susceptibility to complex human diseases or health intervention outcomes; for example, in the emerging fields of pharmacogenomics, nutrigenomics, and vaccinomics. While single nucleotide polymorphisms (SNPs) are frequently employed in these studies, the cost of genotyping a huge number of SNPs remains a limiting factor, particularly in low and middle income countries. Therefore, it is important to detect a subset of SNPs to represent the rest of SNPs with maximum possible accuracy. The present study introduces a new method, CLONTagger with parameter optimization, which uses Support Vector Machine (SVM) to predict the rest of SNPs and Clonal Selection Algorithm (CLONALG) to select tag SNPs. Furthermore, the Particle Swarm Optimization algorithm is preferred for the optimization of C and γ parameters of the Support Vector Machine. Additionally, using many datasets, we compared the proposed new method with the tag SNP selection algorithms present in literature. Our results suggest that the CLONTagger with parameter optimization can identify tag SNPs with better prediction accuracy than other methods. Application-oriented studies are warranted to evaluate the utility of this method in future research in human genetics and study of the genetic components of variable responses to drugs, nutrition, and vaccines.

Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia

“…These observations warrant further mechanistic research, for example, using pharmacogenetic association studies (Ilhan and Tezel, 2013;Wang et al, 2013) so as to identify biomarkers of patients who may be at particular risk for excessive shifts in cardiovascular pharmacodynamics after donepezil treatment.…”

A powerful score-based test statistic for detecting gene-gene co-association

“…In practice, all LD and haplotype block analyses can be achieved by Haploview software [ 29 ]. Furthermore, there are many other methods have been recently proposed, including the weighted tag-SNP-set analytical method [ 30 ], the CLONTagger method [ 31 ], the diSNP selection method [ 32 ] and the FastTagger method [ 33 ]. Meanwhile, it is inevitable to yield very noisy covariance matrices and face multiple testing problems once extending the proposed statistic to a large genome-wide scale, which should be considered in the future.…”

Missense Mutations in the Irak1 Gene Are Associated With an Increased Risk of Systemic Lupus Erythematosus

“…Identifying SNPs in a candidate gene is challenging for thousands of SNPs (Zhernakova et al 2009). Bioinformatic approaches are essential for determining which SNPs can be analyzed based on their functional relevance to distinguish between neutral and SNPs that can affect protein stability (Ilhan & Tezel, 2013;Patnala et al, 2013). In silico methods have been used to determine how genetic sequence differences can affect protein structure and function.…”