Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder

Cichon, Sven, Muehleisen, Thomas W., Degenhardt, Franziska A., Mattheisen, Manuel, Miro, Xavier, Strohmaier, Jana, Steffens, Michael, Meesters, Christian, Herms, Stefan, Weingarten, Moritz, Priebe, Lutz, Haenisch, Britta, Aexander, Michael, Vollmer, Jennifer, Breuer, Rene, Schmael, Christine, Tessmann, Peter, Moebus, Susanne, Wichmann, H. -Erich, Schreiber, Stefan, Mueller-Myhsok, Bertram, Lucae, Susanne, Jamain, Stephane, Leboyer, Marion, Bellivier, Frank, Etain, Bruno, Henry, Chantal, Kahn, Jean-Pierre, Heath, Simon, Hamshere, Marian, O'Donovan, Michael C., Owen, Michael J., Craddock, Nick, Schwarz, Markus, Vedder, Helmut, Kammerer-Ciernioch, Jutta, Reif, Andreas, Sasse, Johanna, Bauer, Michael, Hautzinger, Martin, Wright, Adam, Mitchell, Philip B., Schofield, Peter R., Montgomery, Grant W., Medland, Sarah E., Gordon, Scott D., Martin, Nicholas G., Gustafsson, Omar, Andreassen, Ole, Djurovic, Srdjan, Sigurdsson, Engilbert, Steinberg, Stacy, Stefansson, Hreinn, Stefansson, Kari, Kapur-Pojskic, Lejla, Oruc, Liliana, Rivas, Fabio, Mayoral, Fermin, Chuchalin, Alexander, Babadjanova, Gulja, Tiganov, Alexander S., Pantelejeva, Galina, Abramova, Lilia I., Grigoroiu-Serbanescu, Maria, Diaconu, Carmen C., Czerski, Piotr M., Hauser, Joanna, Zimmer, Andreas, Lathrop, Mark, Schulze, Thomas G., Wienker, Thomas F., Schumacher, Johannes, Maier, Wolfgang, Propping, Peter, Rietschel, Marcella and Noethen, Markus M. (2011) Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. American Journal of Human Genetics, 88 3: 372-381. doi:10.1016/j.ajhg.2011.01.017


Author Cichon, Sven
Muehleisen, Thomas W.
Degenhardt, Franziska A.
Mattheisen, Manuel
Miro, Xavier
Strohmaier, Jana
Steffens, Michael
Meesters, Christian
Herms, Stefan
Weingarten, Moritz
Priebe, Lutz
Haenisch, Britta
Aexander, Michael
Vollmer, Jennifer
Breuer, Rene
Schmael, Christine
Tessmann, Peter
Moebus, Susanne
Wichmann, H. -Erich
Schreiber, Stefan
Mueller-Myhsok, Bertram
Lucae, Susanne
Jamain, Stephane
Leboyer, Marion
Bellivier, Frank
Etain, Bruno
Henry, Chantal
Kahn, Jean-Pierre
Heath, Simon
Hamshere, Marian
O'Donovan, Michael C.
Owen, Michael J.
Craddock, Nick
Schwarz, Markus
Vedder, Helmut
Kammerer-Ciernioch, Jutta
Reif, Andreas
Sasse, Johanna
Bauer, Michael
Hautzinger, Martin
Wright, Adam
Mitchell, Philip B.
Schofield, Peter R.
Montgomery, Grant W.
Medland, Sarah E.
Gordon, Scott D.
Martin, Nicholas G.
Gustafsson, Omar
Andreassen, Ole
Djurovic, Srdjan
Sigurdsson, Engilbert
Steinberg, Stacy
Stefansson, Hreinn
Stefansson, Kari
Kapur-Pojskic, Lejla
Oruc, Liliana
Rivas, Fabio
Mayoral, Fermin
Chuchalin, Alexander
Babadjanova, Gulja
Tiganov, Alexander S.
Pantelejeva, Galina
Abramova, Lilia I.
Grigoroiu-Serbanescu, Maria
Diaconu, Carmen C.
Czerski, Piotr M.
Hauser, Joanna
Zimmer, Andreas
Lathrop, Mark
Schulze, Thomas G.
Wienker, Thomas F.
Schumacher, Johannes
Maier, Wolfgang
Propping, Peter
Rietschel, Marcella
Noethen, Markus M.
Title Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2011-03-11
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2011.01.017
Open Access Status Not yet assessed
Volume 88
Issue 3
Start page 372
End page 381
Total pages 10
Place of publication Cambridge, MA United States
Publisher Cell Press
Language eng
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 x 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 x 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 x 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.
Formatted 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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 01GS08144
42151/2008
POSDRU/89/1.5/S/64109
N N402 244035
ANR NEURO2006
510135
167153/V50
123-2004
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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