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
24026092
TITLE
Genetic and nongenetic variation revealed for the principal components of human gene expression.
ABSTRACT
Principal components analysis has been employed in gene expression studies to correct for population substructure and batch and environmental effects. This method typically involves the removal of variation contained in as many as 50 principal components (PCs), which can constitute a large proportion of total variation present in the data. Each PC, however, can detect many sources of variation, including gene expression networks and genetic variation influencing transcript levels. We demonstrate that PCs generated from gene expression data can simultaneously contain both genetic and nongenetic factors. From heritability estimates we show that all PCs contain a considerable portion of genetic variation while nongenetic artifacts such as batch effects were associated to varying degrees with the first 60 PCs. These PCs demonstrate an enrichment of biological pathways, including core immune function and metabolic pathways. The use of PC correction in two independent data sets resulted in a reduction in the number of cis- and trans-expression QTL detected. Comparisons of PC and linear model correction revealed that PC correction was not as efficient at removing known batch effects and had a higher penalty on genetic variation. Therefore, this study highlights the danger of eliminating biologically relevant data when employing PC correction in gene expression data.
DATE PUBLISHED
2013 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2013/09/11
entrez 2013/09/13 06:00
pubmed 2013/09/13 06:00
medline 2014/06/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Goldinger A Goldinger Anita A University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, Queensland 4102, Australia.
Henders AK Henders Anjali K AK
McRae AF McRae Allan F AF
Martin NG Martin Nicholas G NG
Gibson G Gibson Greg G
Montgomery GW Montgomery Grant W GW
Visscher PM Visscher Peter M PM
Powell JE Powell Joseph E JE
INVESTIGATORS
JOURNAL
VOLUME: 195
ISSUE: 3
TITLE: Genetics
ISOABBREVIATION: Genetics
YEAR: 2013
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1943-2631
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genetics
COUNTRY: United States
ISSNLINKING: 0016-6731
NLMUNIQUEID: 0374636
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
GM057091 NIGMS NIH HHS United States
P01 GM099568 NIGMS NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
batch effects
gene expression
heritability
linear models
normalization
principal components analysis
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Female
Gene Expression Profiling statistics & numerical data
Genetic Variation statistics & numerical data
Genome-Wide Association Study statistics & numerical data
Humans statistics & numerical data
Linear Models statistics & numerical data
Male statistics & numerical data
Models, Genetic statistics & numerical data
Principal Component Analysis statistics & numerical data
Quantitative Trait Loci statistics & numerical data
Quantitative Trait, Heritable statistics & numerical data
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3813841 NLM
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