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
23696747
TITLE
Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.
ABSTRACT
There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.
DATE PUBLISHED
2013 May
HISTORY
PUBSTATUS PUBSTATUSDATE
ppublish 2013/05
received 2012/12/20
accepted 2013/03/22
epublish 2013/05/16
entrez 2013/05/23 06:00
pubmed 2013/05/23 06:00
medline 2013/09/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Powell JE Powell Joseph E JE University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia. joseph.powell@uq.edu.au
Henders AK Henders Anjali K AK
McRae AF McRae Allan F AF
Kim J Kim Jinhee J
Hemani G Hemani Gibran G
Martin NG Martin Nicholas G NG
Dermitzakis ET Dermitzakis Emmanouil T ET
Gibson G Gibson Greg G
Montgomery GW Montgomery Grant W GW
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE: 5
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2013
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
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
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Chromosome Mapping
Female
Gene Expression
Genetic Association Studies
Genetic Predisposition to Disease
Genetics, Population
Humans
Male
Middle Aged
Pedigree
Polymorphism, Single Nucleotide
Quantitative Trait Loci genetics
Twins, Dizygotic genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3656157 NLM