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
21353194
TITLE
Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.
ABSTRACT
We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.
Copyright 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2011 Mar 11
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/10/01
revised 2011/01/14
accepted 2011/01/29
aheadofprint 2011/02/25
entrez 2011/03/01 06:00
pubmed 2011/03/01 06:00
medline 2011/05/17 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cichon S Cichon Sven S Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany. sven.cichon@uni-bonn.de
Mühleisen TW Mühleisen Thomas W TW
Degenhardt FA Degenhardt Franziska A FA
Mattheisen M Mattheisen Manuel M
Miró X Miró Xavier X
Strohmaier J Strohmaier Jana J
Steffens M Steffens Michael M
Meesters C Meesters Christian C
Herms S Herms Stefan S
Weingarten M Weingarten Moritz M
Priebe L Priebe Lutz L
Haenisch B Haenisch Britta B
Alexander M Alexander Michael M
Vollmer J Vollmer Jennifer J
Breuer R Breuer René R
Schmäl C Schmäl Christine C
Tessmann P Tessmann Peter P
Moebus S Moebus Susanne S
Wichmann HE Wichmann H-Erich HE
Schreiber S Schreiber Stefan S
Müller-Myhsok B Müller-Myhsok Bertram B
Lucae S Lucae Susanne S
Jamain S Jamain Stéphane S
Leboyer M Leboyer Marion M
Bellivier F Bellivier Frank F
Etain B Etain Bruno B
Henry C Henry Chantal C
Kahn JP Kahn Jean-Pierre JP
Heath S Heath Simon S
Bipolar Disorder Genome Study (BiGS) Consortium
Hamshere M Hamshere Marian M
O'Donovan MC O'Donovan Michael C MC
Owen MJ Owen Michael J MJ
Craddock N Craddock Nick N
Schwarz M Schwarz Markus M
Vedder H Vedder Helmut H
Kammerer-Ciernioch J Kammerer-Ciernioch Jutta J
Reif A Reif Andreas A
Sasse J Sasse Johanna J
Bauer M Bauer Michael M
Hautzinger M Hautzinger Martin M
Wright A Wright Adam A
Mitchell PB Mitchell Philip B PB
Schofield PR Schofield Peter R PR
Montgomery GW Montgomery Grant W GW
Medland SE Medland Sarah E SE
Gordon SD Gordon Scott D SD
Martin NG Martin Nicholas G NG
Gustafsson O Gustafsson Omar O
Andreassen O Andreassen Ole O
Djurovic S Djurovic Srdjan S
Sigurdsson E Sigurdsson Engilbert E
Steinberg S Steinberg Stacy S
Stefansson H Stefansson Hreinn H
Stefansson K Stefansson Kari K
Kapur-Pojskic L Kapur-Pojskic Lejla L
Oruc L Oruc Liliana L
Rivas F Rivas Fabio F
Mayoral F Mayoral Fermín F
Chuchalin A Chuchalin Alexander A
Babadjanova G Babadjanova Gulja G
Tiganov AS Tiganov Alexander S AS
Pantelejeva G Pantelejeva Galina G
Abramova LI Abramova Lilia I LI
Grigoroiu-Serbanescu M Grigoroiu-Serbanescu Maria M
Diaconu CC Diaconu Carmen C CC
Czerski PM Czerski Piotr M PM
Hauser J Hauser Joanna J
Zimmer A Zimmer Andreas A
Lathrop M Lathrop Mark M
Schulze TG Schulze Thomas G TG
Wienker TF Wienker Thomas F TF
Schumacher J Schumacher Johannes J
Maier W Maier Wolfgang W
Propping P Propping Peter P
Rietschel M Rietschel Marcella M
Nöthen MM Nöthen Markus M MM
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Kelsoe John R JR
Greenwood Tiffany A TA
Nievergelt Caroline M CM
Barrett Thomas B TB
McKinney Rebecca R
Shilling Paul D PD
Schork Nicholas J NJ
Smith Erin N EN
Bloss Cinnamon S CS
Nurnberger John J
Edenberg Howard J HJ
Foroud Tatiana T
Koller Daniel L DL
Gershon Elliot S ES
Liu Chun-Yu CY
Badner Judith A JA
Scheftner William W
Lawson William B WB
Nwulia Evaristus A EA
Hipolito Maria M
Coryell William W
Rice John J
Byerley William W
McMahon Francis F
Schulze Thomas G TG
Berrettini Wade W
Potash James B JB
Zandi Peter B PB
Mahon Pamela B PB
McInnis Melvin M
Craig David D
Szelinger Szabolcs S
JOURNAL
VOLUME: 88
ISSUE: 3
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2011
MONTH: Mar
DAY: 11
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Mol Cell Biol. 2001 Sep;21(17):5970-8 11486035
Cites Mol Psychiatry. 2009 Aug;14(8):755-63 19488044
Cites Am Heart J. 2002 Aug;144(2):212-8 12177636
Cites Arch Gen Psychiatry. 1978 Jun;35(6):773-82 655775
Cites Arch Gen Psychiatry. 1978 Jul;35(7):837-44 678037
Cites Arch Gen Psychiatry. 1982 Aug;39(8):879-83 7103676
Cites Nucleic Acids Res. 1988 Feb 11;16(3):1215 3344216
Cites Arch Gen Psychiatry. 1990 Jun;47(6):589-93 2190539
Cites Arch Gen Psychiatry. 1992 Aug;49(8):624-9 1637252
Cites J Biol Chem. 1992 Sep 25;267(27):19536-47 1326557
Cites Br J Psychiatry. 1992 Dec;161:824-30 1483169
Cites Arch Gen Psychiatry. 1994 Nov;51(11):849-59; discussion 863-4 7944874
Cites JAMA. 1994 Dec 14;272(22):1749-56 7966923
Cites Eur J Neurosci. 1995 Apr 1;7(4):547-54 7620606
Cites Psychol Med. 1995 Nov;25(6):1269-80 8637956
Cites Psychol Med. 1996 Nov;26(6):1169-77 8931163
Cites J Biol Chem. 1998 Aug 21;273(34):21439-42 9705269
Cites Hum Hered. 2004;58(3-4):122-30 15812168
Cites Gesundheitswesen. 2005 Aug;67 Suppl 1:S26-30 16032514
Cites Nature. 2005 Oct 27;437(7063):1299-320 16255080
Cites Community Genet. 2006;9(1):55-61 16490960
Cites Cancer Res. 2007 Jan 1;67(1):160-6 17210695
Cites Science. 2007 Jun 1;316(5829):1331-6 17463246
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Behav Pharmacol. 2007 Sep;18(5-6):419-30 17762510
Cites Mol Psychiatry. 2008 Feb;13(2):197-207 17486107
Cites Mol Psychiatry. 2008 May;13(5):466-7 18421293
Cites Mol Psychiatry. 2008 Jun;13(6):558-69 18317468
Cites Hum Mol Genet. 2008 Oct 15;17(R2):R122-8 18852200
Cites Bioinformatics. 2008 Dec 15;24(24):2938-9 18974171
Cites Nat Genet. 2008 Sep;40(9):1056-8 18711365
Cites Science. 2009 Mar 13;323(5920):1477-81 19286556
Cites J Clin Invest. 2009 Apr;119(4):726-36 19339764
Cites Mol Psychiatry. 2009 May;14(5):487-91 19088739
Cites Proc Natl Acad Sci U S A. 2009 May 5;106(18):7501-6 19416921
Cites Dis Model Mech. 2009 Jul-Aug;2(7-8):412-8 19535498
ErratumIn Am J Hum Genet. 2011 Mar 11;88(3):396 19535498
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Animals
Bipolar Disorder genetics
Brain pathology
Case-Control Studies pathology
Follow-Up Studies pathology
Genetic Predisposition to Disease pathology
Genetic Variation pathology
Genome-Wide Association Study pathology
Humans pathology
Mice pathology
Neurocan genetics
Polymorphism, Single Nucleotide genetics
Reproducibility of Results genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Neurocan
OTHER ID's
OTHERID SOURCE
PMC3059436 NLM