Abstract
We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10 -7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 977-985 |
| Number of pages | 9 |
| Journal | Nature genetics |
| Volume | 43 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2011 |
ASJC Scopus subject areas
- Genetics
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Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. / Sklar, Pamela; Ripke, Stephan; Scott, Laura J.; Andreassen, Ole A.; Cichon, Sven; Craddock, Nick; Edenberg, Howard J.; Nurnberger, John I.; Rietschel, Marcella; Blackwood, Douglas; Corvin, Aiden; Flickinger, Matthew; Guan, Weihua; Mattingsdal, Morten; McQuillin, Andrew; Kwan, Phoenix; Wienker, Thomas F.; Daly, Mark; Dudbridge, Frank; Holmans, Peter A.; Lin, Danyu; Burmeister, Margit; Greenwood, Tiffany A.; Hamshere, Marian L.; Muglia, Pierandrea; Smith, Erin N.; Zandi, Peter P.; Nievergelt, Caroline M.; McKinney, Rebecca; Shilling, Paul D.; Schork, Nicholas J.; Bloss, Cinnamon S.; Foroud, Tatiana; Koller, Daniel L.; Gershon, Elliot S.; Liu, Chunyu; Badner, Judith A.; Scheftner, William A.; Lawson, William B.; Nwulia, Evaristus A.; Hipolito, Maria; Coryell, William; Rice, John; Byerley, William; McMahon, Francis J.; Schulze, Thomas G.; Berrettini, Wade; Lohoff, Falk W.; Potash, James B.; Mahon, Pamela B.; McInnis, Melvin G.; Zöllner, Sebastian; Zhang, Peng; Craig, David W.; Szelinger, Szabocls; Barrett, Thomas B.; Breuer, René; Meier, Sandra; Strohmaier, Jana; Witt, Stephanie H.; Tozzi, Federica; Farmer, Anne; McGuffin, Peter; Strauss, John; Xu, Wei; Kennedy, James L.; Vincent, John B.; Matthews, Keith; Day, Richard; Ferreira, Manuel A.; O'Dushlaine, Colm; Perlis, Roy; Raychaudhuri, Soumya; Ruderfer, Douglas; Lee, Phil H.; Smoller, Jordan W.; Li, Jun; Absher, Devin; Bunney, William E.; Barchas, Jack D.; Schatzberg, Alan F.; Jones, Edward G.; Meng, Fan; Thompson, Robert C.; Watson, Stanley J.; Myers, Richard M.; Akil, Huda; Boehnke, Michael; Chambert, Kim; Moran, Jennifer; Scolnick, Ed; Djurovic, Srdjan; Melle, Ingrid; Morken, Gunnar; Gill, Michael; Morris, Derek; Quinn, Emma; Mühleisen, Thomas W.; Degenhardt, Franziska A.; Mattheisen, Manuel; Schumacher, Johannes; Maier, Wolfgang; Steffens, Michael; Propping, Peter; Nöthen, Markus M.; Anjorin, Adebayo; Bass, Nick; Gurling, Hugh; Kandaswamy, Radhika; Lawrence, Jacob; McGhee, Kevin; McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.; Breen, Gerome; St. Clair, David; Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa; Fraser, Christine; Green, Elaine K.; Grozeva, Detelina; Jones, Ian R.; Kirov, George; Moskvina, Valentina; Nikolov, Ivan; O'Donovan, Michael C.; Owen, Michael J.; Collier, David A.; Elkin, Amanda; Williamson, Richard; Young, Allan H.; Nicol Ferrier, I.; Stefansson, Kari; Stefansson, Hreinn; Porgeirsson, Porgeir; Steinberg, Stacy; Gustafsson, Ómar; Bergen, Sarah E.; Nimgaonkar, Vishwajit; Hultman, Christina; Landén, Mikael; Lichtenstein, Paul; Sullivan, Patrick; Schalling, Martin; Osby, Urban; Backlund, Lena; Frisén, Louise; Langstrom, Niklas; Jamain, Stéphane; Leboyer, Marion; Etain, Bruno; Bellivier, Frank; Petursson, Hannes; Sigurdsson, Engilbert; Müller-Mysok, Bertram; Lucae, Susanne; Schwarz, Markus; Fullerton, Janice M.; Schofield, Peter R.; Martin, Nick; Montgomery, Grant W.; Lathrop, Mark; Óskarsson, Högni; Bauer, Michael; Wright, Adam; Mitchell, Philip B.; Hautzinger, Martin; Reif, Andreas; Kelsoe, John R.; Purcell, Shaun M.
In: Nature genetics, Vol. 43, No. 10, 10.2011, p. 977-985.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4
AU - Sklar, Pamela
AU - Ripke, Stephan
AU - Scott, Laura J.
AU - Andreassen, Ole A.
AU - Cichon, Sven
AU - Craddock, Nick
AU - Edenberg, Howard J.
AU - Nurnberger, John I.
AU - Rietschel, Marcella
AU - Blackwood, Douglas
AU - Corvin, Aiden
AU - Flickinger, Matthew
AU - Guan, Weihua
AU - Mattingsdal, Morten
AU - McQuillin, Andrew
AU - Kwan, Phoenix
AU - Wienker, Thomas F.
AU - Daly, Mark
AU - Dudbridge, Frank
AU - Holmans, Peter A.
AU - Lin, Danyu
AU - Burmeister, Margit
AU - Greenwood, Tiffany A.
AU - Hamshere, Marian L.
AU - Muglia, Pierandrea
AU - Smith, Erin N.
AU - Zandi, Peter P.
AU - Nievergelt, Caroline M.
AU - McKinney, Rebecca
AU - Shilling, Paul D.
AU - Schork, Nicholas J.
AU - Bloss, Cinnamon S.
AU - Foroud, Tatiana
AU - Koller, Daniel L.
AU - Gershon, Elliot S.
AU - Liu, Chunyu
AU - Badner, Judith A.
AU - Scheftner, William A.
AU - Lawson, William B.
AU - Nwulia, Evaristus A.
AU - Hipolito, Maria
AU - Coryell, William
AU - Rice, John
AU - Byerley, William
AU - McMahon, Francis J.
AU - Schulze, Thomas G.
AU - Berrettini, Wade
AU - Lohoff, Falk W.
AU - Potash, James B.
AU - Mahon, Pamela B.
AU - McInnis, Melvin G.
AU - Zöllner, Sebastian
AU - Zhang, Peng
AU - Craig, David W.
AU - Szelinger, Szabocls
AU - Barrett, Thomas B.
AU - Breuer, René
AU - Meier, Sandra
AU - Strohmaier, Jana
AU - Witt, Stephanie H.
AU - Tozzi, Federica
AU - Farmer, Anne
AU - McGuffin, Peter
AU - Strauss, John
AU - Xu, Wei
AU - Kennedy, James L.
AU - Vincent, John B.
AU - Matthews, Keith
AU - Day, Richard
AU - Ferreira, Manuel A.
AU - O'Dushlaine, Colm
AU - Perlis, Roy
AU - Raychaudhuri, Soumya
AU - Ruderfer, Douglas
AU - Lee, Phil H.
AU - Smoller, Jordan W.
AU - Li, Jun
AU - Absher, Devin
AU - Bunney, William E.
AU - Barchas, Jack D.
AU - Schatzberg, Alan F.
AU - Jones, Edward G.
AU - Meng, Fan
AU - Thompson, Robert C.
AU - Watson, Stanley J.
AU - Myers, Richard M.
AU - Akil, Huda
AU - Boehnke, Michael
AU - Chambert, Kim
AU - Moran, Jennifer
AU - Scolnick, Ed
AU - Djurovic, Srdjan
AU - Melle, Ingrid
AU - Morken, Gunnar
AU - Gill, Michael
AU - Morris, Derek
AU - Quinn, Emma
AU - Mühleisen, Thomas W.
AU - Degenhardt, Franziska A.
AU - Mattheisen, Manuel
AU - Schumacher, Johannes
AU - Maier, Wolfgang
AU - Steffens, Michael
AU - Propping, Peter
AU - Nöthen, Markus M.
AU - Anjorin, Adebayo
AU - Bass, Nick
AU - Gurling, Hugh
AU - Kandaswamy, Radhika
AU - Lawrence, Jacob
AU - McGhee, Kevin
AU - McIntosh, Andrew
AU - McLean, Alan W.
AU - Muir, Walter J.
AU - Pickard, Benjamin S.
AU - Breen, Gerome
AU - St. Clair, David
AU - Caesar, Sian
AU - Gordon-Smith, Katherine
AU - Jones, Lisa
AU - Fraser, Christine
AU - Green, Elaine K.
AU - Grozeva, Detelina
AU - Jones, Ian R.
AU - Kirov, George
AU - Moskvina, Valentina
AU - Nikolov, Ivan
AU - O'Donovan, Michael C.
AU - Owen, Michael J.
AU - Collier, David A.
AU - Elkin, Amanda
AU - Williamson, Richard
AU - Young, Allan H.
AU - Nicol Ferrier, I.
AU - Stefansson, Kari
AU - Stefansson, Hreinn
AU - Porgeirsson, Porgeir
AU - Steinberg, Stacy
AU - Gustafsson, Ómar
AU - Bergen, Sarah E.
AU - Nimgaonkar, Vishwajit
AU - Hultman, Christina
AU - Landén, Mikael
AU - Lichtenstein, Paul
AU - Sullivan, Patrick
AU - Schalling, Martin
AU - Osby, Urban
AU - Backlund, Lena
AU - Frisén, Louise
AU - Langstrom, Niklas
AU - Jamain, Stéphane
AU - Leboyer, Marion
AU - Etain, Bruno
AU - Bellivier, Frank
AU - Petursson, Hannes
AU - Sigurdsson, Engilbert
AU - Müller-Mysok, Bertram
AU - Lucae, Susanne
AU - Schwarz, Markus
AU - Fullerton, Janice M.
AU - Schofield, Peter R.
AU - Martin, Nick
AU - Montgomery, Grant W.
AU - Lathrop, Mark
AU - Óskarsson, Högni
AU - Bauer, Michael
AU - Wright, Adam
AU - Mitchell, Philip B.
AU - Hautzinger, Martin
AU - Reif, Andreas
AU - Kelsoe, John R.
AU - Purcell, Shaun M.
N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2011/10
Y1 - 2011/10
N2 - We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10 -7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
AB - We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10 -7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
UR - http://www.scopus.com/inward/record.url?scp=80053385384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053385384&partnerID=8YFLogxK
U2 - 10.1038/ng.943
DO - 10.1038/ng.943
M3 - Article
C2 - 21926972
AN - SCOPUS:80053385384
VL - 43
SP - 977
EP - 985
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 10
ER -