alexa Extending rare-variant testing strategies: analysis of noncoding sequence and imputed genotypes.
Genetics & Molecular Biology

Genetics & Molecular Biology

Human Genetics & Embryology

Author(s): Zawistowski M, Gopalakrishnan S, Ding J, Li Y, Grimm S,

Abstract Share this page

Abstract Next Generation Sequencing Technology has revolutionized our ability to study the contribution of rare genetic variation to heritable traits. However, existing single-marker association tests are underpowered for detecting rare risk variants. A more powerful approach involves pooling methods that combine multiple rare variants from the same gene into a single test statistic. Proposed pooling methods can be limited because they generally assume high-quality genotypes derived from deep-coverage sequencing, which may not be available. In this paper, we consider an intuitive and computationally efficient pooling statistic, the cumulative minor-allele test (CMAT). We assess the performance of the CMAT and other pooling methods on datasets simulated with population genetic models to contain realistic levels of neutral variation. We consider study designs ranging from exon-only to whole-gene analyses that contain noncoding variants. For all study designs, the CMAT achieves power comparable to that of previously proposed methods. We then extend the CMAT to probabilistic genotypes and describe application to low-coverage sequencing and imputation data. We show that augmenting sequence data with imputed samples is a practical method for increasing the power of rare-variant studies. We also provide a method of controlling for confounding variables such as population stratification. Finally, we demonstrate that our method makes it possible to use external imputation templates to analyze rare variants imputed into existing GWAS datasets. As proof of principle, we performed a CMAT analysis of more than 8 million SNPs that we imputed into the GAIN psoriasis dataset by using haplotypes from the 1000 Genomes Project. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
This article was published in Am J Hum Genet and referenced in Human Genetics & Embryology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords