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
17667963
TITLE
A whole genome association study of neuroticism using DNA pooling.
ABSTRACT
We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from approximately 2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings. We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, the SNP was not significantly associated with neuroticism in two other independent samples. We also observed an enrichment of low P-values in known regions of copy number variations. Simulation indicates that our study had approximately 80% power to identify neuroticism loci in the genome with odds ratio (OR)>2, and approximately 50% power to identify small effects (OR=1.5). Since we failed to find any loci accounting for more than 1% of the variance, the heritability of neuroticism probably arises from many loci each explaining much less than 1%. Our findings argue the need for much larger samples than anticipated in genetic association studies and that the biological basis of emotional disorders is extremely complex.
DATE PUBLISHED
2008 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2007/07/31
pubmed 2007/08/02 09:00
medline 2008/04/18 09:00
entrez 2007/08/02 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Shifman S Shifman S S Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Bhomra A Bhomra A A
Smiley S Smiley S S
Wray NR Wray N R NR
James MR James M R MR
Martin NG Martin N G NG
Hettema JM Hettema J M JM
An SS An S S SS
Neale MC Neale M C MC
van den Oord EJ van den Oord E J C G EJ
Kendler KS Kendler K S KS
Chen X Chen X X
Boomsma DI Boomsma D I DI
Middeldorp CM Middeldorp C M CM
Hottenga JJ Hottenga J J JJ
Slagboom PE Slagboom P E PE
Flint J Flint J J
INVESTIGATORS
JOURNAL
VOLUME: 13
ISSUE: 3
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2008
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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CommentIn Mol Psychiatry. 2008 Sep;13(9):831-2 18711446
GRANTS
GRANTID AGENCY COUNTRY
079912 Wellcome Trust United Kingdom
R01 DA018673 NIDA NIH HHS United States
R37 DA018673 NIDA NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cohort Studies
Computer Simulation
Cyclic Nucleotide Phosphodiesterases, Type 4 genetics
Female genetics
Gene Frequency genetics
Genetic Markers genetics
Genetic Predisposition to Disease genetics
Genome physiology
Genotype physiology
Humans physiology
Linkage Disequilibrium physiology
Male physiology
Mass Screening methods
Neurotic Disorders genetics
Oligonucleotide Array Sequence Analysis genetics
Personality Inventory genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
EC 3.1.4.17 Cyclic Nucleotide Phosphodiesterases, Type 4
OTHER ID's
OTHERID SOURCE
NIHMS572905 NLM
PMC4004964 NLM
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