Genetic Epidemiology, Psychiatric Genetics, Asthma 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
27048375
TITLE
Shared genetic control of expression and methylation in peripheral blood.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Expression QTLs and epigenetic marks are often employed to provide an insight into the possible biological mechanisms behind GWAS hits. A substantial proportion of the variation in gene expression and DNA methylation is known to be under genetic control. We address the proportion of genetic control that is shared between these two genomic features.
RESULTS NlmCategory: RESULTS
An exhaustive search for pairwise phenotypic correlations between gene expression and DNA methylation in samples from human blood (n = 610) was performed. Of the 5 × 10(9) possible pairwise tests, 0.36 % passed Bonferroni corrected p-value cutoff of 9.9 × 10(-12). We determined that the correlation structure between probe pairs was largely due to blood cell type specificity of the expression and methylation probes. Upon adjustment of the expression and methylation values for observed blood cellular composition (n = 422), the number of probe pairs which survived Bonferroni correction reduced by more than 5400 fold. Of the 614 correlated probe pairs located on the same chromosome, 75 % share at least one methylation and expression QTL at nominal 10(-5) p-value cutoff. Those probe pairs are located within 1Mbp window from each other and have a mean of absolute value of genetic correlation equal to 0.69, further demonstrating the high degree of shared genetic control.
CONCLUSIONS NlmCategory: CONCLUSIONS
Overall, this study demonstrates notable genetic covariance between DNA methylation and gene expression and reaffirms the importance of correcting for cell-counts in studies on non-homogeneous tissues.
DATE PUBLISHED
2016
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/07/16
accepted 2016/02/17
aheadofprint 2016/04/06
entrez 2016/04/07 06:00
pubmed 2016/04/07 06:00
medline 2016/04/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Shakhbazov K Shakhbazov Konstantin K Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. konstantin.shakhbazov@gmail.com.
Powell JE Powell Joseph E JE QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, QLD, Australia.
Hemani G Hemani Gibran G Current address: MRC Integrative Epidemiology Unit and School of Social and Community Medicine, University of Bristol, Bristol, BS8 2BN, UK.
Henders AK Henders Anjali K AK Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, QLD, Australia.
Visscher PM Visscher Peter M PM University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, QLD, Australia.
McRae AF McRae Allan F AF University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
INVESTIGATORS
JOURNAL
VOLUME: 17
ISSUE: 1
TITLE: BMC genomics
ISOABBREVIATION: BMC Genomics
YEAR: 2016
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1471-2164
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: BMC Genomics
COUNTRY: England
ISSNLINKING: 1471-2164
NLMUNIQUEID: 100965258
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
DNA methylation
Gene expression
Genetic correlation
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC4822256 NLM