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
18317468
TITLE
Whole-genome association study of bipolar disorder.
ABSTRACT
We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.
DATE PUBLISHED
2008 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/03/04
pubmed 2008/03/05 09:00
medline 2008/08/07 09:00
entrez 2008/03/05 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Sklar P Sklar P P Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. sklar@chgr.mgh.harvard.edu
Smoller JW Smoller J W JW
Fan J Fan J J
Ferreira MA Ferreira M A R MA
Perlis RH Perlis R H RH
Chambert K Chambert K K
Nimgaonkar VL Nimgaonkar V L VL
McQueen MB McQueen M B MB
Faraone SV Faraone S V SV
Kirby A Kirby A A
de Bakker PI de Bakker P I W PI
Ogdie MN Ogdie M N MN
Thase ME Thase M E ME
Sachs GS Sachs G S GS
Todd-Brown K Todd-Brown K K
Gabriel SB Gabriel S B SB
Sougnez C Sougnez C C
Gates C Gates C C
Blumenstiel B Blumenstiel B B
Defelice M Defelice M M
Ardlie KG Ardlie K G KG
Franklin J Franklin J J
Muir WJ Muir W J WJ
McGhee KA McGhee K A KA
MacIntyre DJ MacIntyre D J DJ
McLean A McLean A A
VanBeck M VanBeck M M
McQuillin A McQuillin A A
Bass NJ Bass N J NJ
Robinson M Robinson M M
Lawrence J Lawrence J J
Anjorin A Anjorin A A
Curtis D Curtis D D
Scolnick EM Scolnick E M EM
Daly MJ Daly M J MJ
Blackwood DH Blackwood D H DH
Gurling HM Gurling H M HM
Purcell SM Purcell S M SM
INVESTIGATORS
JOURNAL
VOLUME: 13
ISSUE: 6
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2008
MONTH: Jun
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, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
066717 Wellcome Trust United Kingdom
G0500791 Medical Research Council United Kingdom
G9623693N Medical Research Council United Kingdom
MH059565 NIMH NIH HHS United States
MH059571 NIMH NIH HHS United States
MH059588 NIMH NIH HHS United States
MH061675 NIMH NIH HHS United States
MH062137 NIMH NIH HHS United States
MH063445 NIMH NIH HHS United States
MH067257 NIMH NIH HHS United States
MH067288 NIMH NIH HHS United States
MH59566 NIMH NIH HHS United States
MH59586 NIMH NIH HHS United States
MH59587 NIMH NIH HHS United States
MH60870 NIMH NIH HHS United States
MH63420 NIMH NIH HHS United States
N01MH80001 NIMH NIH HHS United States
R01 HD060726 NICHD NIH HHS United States
R01 MH059534 NIMH NIH HHS United States
R01 MH059548 NIMH NIH HHS United States
R01 MH059556 NIMH NIH HHS United States
R01 MH59533 NIMH NIH HHS United States
R01 MH59535 NIMH NIH HHS United States
R01 MH59545 NIMH NIH HHS United States
R01 MH59553 NIMH NIH HHS United States
R01 MH59567 NIMH NIH HHS United States
R01 MH60068 NIMH NIH HHS United States
RC2 MH089905 NIMH NIH HHS United States
U01 MH060879 NIMH NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Antigens, Neoplasm genetics
Bipolar Disorder genetics
Chromosome Mapping genetics
DNA isolation & purification
Gene Frequency isolation & purification
Genetic Markers isolation & purification
Genome, Human isolation & purification
Genotype isolation & purification
Humans isolation & purification
Medical History Taking isolation & purification
Membrane Glycoproteins genetics
Myosin Heavy Chains genetics
Myosin Type V genetics
Patient Selection genetics
Polymorphism, Single Nucleotide genetics
Receptor, Epidermal Growth Factor genetics
Reference Values genetics
Tetraspanins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Antigens, Neoplasm
0 Genetic Markers
0 MYO5B protein, human
0 Membrane Glycoproteins
0 TSPAN8 protein, human
0 Tetraspanins
9007-49-2 DNA
EC 2.7.10.1 Receptor, Epidermal Growth Factor
EC 3.6.1.- Myosin Type V
EC 3.6.4.1 Myosin Heavy Chains
OTHER ID's
OTHERID SOURCE
NIHMS418738 NLM
PMC3777816 NLM
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