A versatile gene-based test for genome-wide association studies

Liu, J. Z., McRae, A. F., Nyholt, D.R., Medland, S. E., Wray, N. R., Brown, K. M., Investigators, Amfs, Hayward, N. K., Montgomery, G. W., Visscher, P. M., Martin, N. G., & Macgregor, S. (2010) A versatile gene-based test for genome-wide association studies. American Journal of Human Genetics, 87(1), pp. 139-145.

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Abstract

We have derived a versatile gene-based test for genome-wide association studies (GWAS). Our approach, called VEGAS (versatile gene-based association study), is applicable to all GWAS designs, including family-based GWAS, meta-analyses of GWAS on the basis of summary data, and DNA-pooling-based GWAS, where existing approaches based on permutation are not possible, as well as singleton data, where they are. The test incorporates information from a full set of markers (or a defined subset) within a gene and accounts for linkage disequilibrium between markers by using simulations from the multivariate normal distribution. We show that for an association study using singletons, our approach produces results equivalent to those obtained via permutation in a fraction of the computation time. We demonstrate proof-of-principle by using the gene-based test to replicate several genes known to be associated on the basis of results from a family-based GWAS for height in 11,536 individuals and a DNA-pooling-based GWAS for melanoma in approximately 1300 cases and controls. Our method has the potential to identify novel associated genes; provide a basis for selecting SNPs for replication; and be directly used in network (pathway) approaches that require per-gene association test statistics. We have implemented the approach in both an easy-to-use web interface, which only requires the uploading of markers with their association p-values, and a separate downloadable application.

Impact and interest:

380 citations in Scopus
372 citations in Web of Science®
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ID Code: 91978
Item Type: Journal Article
Refereed: Yes
Additional Information: Liu, Jimmy Z
McRae, Allan F
Nyholt, Dale R
Medland, Sarah E
Wray, Naomi R
Brown, Kevin M
Hayward, Nicholas K
Montgomery, Grant W
Visscher, Peter M
Martin, Nicholas G
Macgregor, Stuart
eng
CA083115/CA/NCI NIH HHS/
CA109544/CA/NCI NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
2010/07/06 06:00
Am J Hum Genet. 2010 Jul 9;87(1):139-45. doi: 10.1016/j.ajhg.2010.06.009.
Keywords: Case-Control Studies, Genetic Markers, Genome-Wide Association Study/*methods, Humans, Melanoma/genetics, Meta-Analysis as Topic, Multivariate Analysis, Polymorphism, Single Nucleotide, Skin Neoplasms/genetics
DOI: 10.1016/j.ajhg.2010.06.009
ISSN: 0002-9297
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 by The American Society of Human Genetics
Deposited On: 18 Jan 2016 00:44
Last Modified: 15 Feb 2016 22:47

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