Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
20598278
TITLE
A versatile gene-based test for genome-wide association studies.
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.
Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2010 Jul 09
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/04/29
revised 2010/06/07
accepted 2010/06/11
entrez 2010/07/06 06:00
pubmed 2010/07/06 06:00
medline 2010/07/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Liu JZ Liu Jimmy Z JZ Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia. jimmy.liu@uqconnect.edu.au
McRae AF McRae Allan F AF
Nyholt DR Nyholt Dale R DR
Medland SE Medland Sarah E SE
Wray NR Wray Naomi R NR
Brown KM Brown Kevin M KM
AMFS Investigators
Hayward NK Hayward Nicholas K NK
Montgomery GW Montgomery Grant W GW
Visscher PM Visscher Peter M PM
Martin NG Martin Nicholas G NG
Macgregor S Macgregor Stuart S
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Mann Graham J GJ
Kefford Richard F RF
Hopper John L JL
Aitken Joanne F JF
Giles Graham G GG
Armstrong Bruce K BK
JOURNAL
VOLUME: 87
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am J Hum Genet
YEAR: 2010
MONTH: Jul
DAY: 09
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
R01 CA083115 NCI NIH HHS United States
R01 CA109544 NCI NIH HHS United States
CA083115 NCI NIH HHS United States
CA109544 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Case-Control Studies
Genetic Markers
Genome-Wide Association Study methods
Humans methods
Melanoma genetics
Meta-Analysis as Topic genetics
Multivariate Analysis genetics
Polymorphism, Single Nucleotide genetics
Skin Neoplasms genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
OTHER ID's