Dataset Information

A quality control algorithm for filtering SNPs in genome-wide association studies.

ABSTRACT:

Motivation

The quality control (QC) filtering of single nucleotide polymorphisms (SNPs) is an important step in genome-wide association studies to minimize potential false findings. SNP QC commonly uses expert-guided filters based on QC variables [e.g. Hardy-Weinberg equilibrium, missing proportion (MSP) and minor allele frequency (MAF)] to remove SNPs with insufficient genotyping quality. The rationale of the expert filters is sensible and concrete, but its implementation requires arbitrary thresholds and does not jointly consider all QC features.

Results

We propose an algorithm that is based on principal component analysis and clustering analysis to identify low-quality SNPs. The method minimizes the use of arbitrary cutoff values, allows a collective consideration of the QC features and provides conditional thresholds contingent on other QC variables (e.g. different MSP thresholds for different MAFs). We apply our method to the seven studies from the Wellcome Trust Case Control Consortium and the major depressive disorder study from the Genetic Association Information Network. We measured the performance of our method compared to the expert filters based on the following criteria: (i) percentage of SNPs excluded due to low quality; (ii) inflation factor of the test statistics (lambda); (iii) number of false associations found in the filtered dataset; and (iv) number of true associations missed in the filtered dataset. The results suggest that with the same or fewer SNPs excluded, the proposed algorithm tends to give a similar or lower value of lambda, a reduced number of false associations, and retains all true associations.

Availability

The algorithm is available at http://www4.stat.ncsu.edu/jytzeng/software.php

SUBMITTER: Pongpanich M

PROVIDER: S-EPMC2894516 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Publications

A quality control algorithm for filtering SNPs in genome-wide association studies.

Pongpanich Monnat M Sullivan Patrick F PF Tzeng Jung-Ying JY

Bioinformatics (Oxford, England) 20100525 14

<h4>Motivation</h4>The quality control (QC) filtering of single nucleotide polymorphisms (SNPs) is an important step in genome-wide association studies to minimize potential false findings. SNP QC commonly uses expert-guided filters based on QC variables [e.g. Hardy-Weinberg equilibrium, missing proportion (MSP) and minor allele frequency (MAF)] to remove SNPs with insufficient genotyping quality. The rationale of the expert filters is sensible and concrete, but its implementation requires arbit ...[more]

PMID: 20501555

Similar Datasets

Project description:BackgroundRecently mixed linear models are used to address the issue of "missing" heritability in traditional Genome-wide association studies (GWAS). The models assume that all single-nucleotide polymorphisms (SNPs) are associated with the phenotypes of interest. However, it is more common that only a small proportion of SNPs have significant effects on the phenotypes, while most SNPs have no or very small effects. To incorporate this feature, we propose an efficient Hierarchical Bayesian Model (HBM) that extends the existing mixed models to enforce automatic selection of significant SNPs. The HBM models the SNP effects using a mixture distribution of a point mass at zero and a normal distribution, where the point mass corresponds to those non-associative SNPs.ResultsWe estimate the HBM using Gibbs sampling. The estimation performance of our method is first demonstrated through two simulation studies. We make the simulation setups realistic by using parameters fitted on the Framingham Heart Study (FHS) data. The simulation studies show that our method can accurately estimate the proportion of SNPs associated with the simulated phenotype and identify these SNPs, as well as adapt to certain model mis-specification than the standard mixed models. In addition, we analyze data from the FHS and the Health and Retirement Study (HRS) to study the association between Body Mass Index (BMI) and SNPs on Chromosome 16, and replicate the identified genetic associations. The analysis of the FHS data identifies 0.3% SNPs on Chromosome 16 that affect BMI, including rs9939609 and rs9939973 on the FTO gene. These two SNPs are in strong linkage disequilibrium with rs1558902 (Rsq =0.901 for rs9939609 and Rsq =0.905 for rs9939973), which has been reported to be linked with obesity in previous GWAS. We then replicate the findings using the HRS data: the analysis finds 0.4% of SNPs associated with BMI on Chromosome 16. Furthermore, around 25% of the genes that are identified to be associated with BMI are common between the two studies.ConclusionsThe results demonstrate that the HBM and the associated estimation algorithm offer a powerful tool for identifying significant genetic associations with phenotypes of interest, among a large number of SNPs that are common in modern genetics studies.

Dataset Information

A quality control algorithm for filtering SNPs in genome-wide association studies.

Motivation

Results

Availability

Publications

A quality control algorithm for filtering SNPs in genome-wide association studies.

Similar Datasets

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