Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

Hdl Handle:
http://hdl.handle.net/10147/238795
Title:
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
Authors:
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; Hyoun, Phil L; Smoller, Jordan W; Li, Jun; Absher, Devin; Thompson, Robert C; Meng, Fan Guo; Schatzberg, Alan F; Bunney, William E; Barchas, Jack D; Jones, Edward G; 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; Ferrier, I Nicol; Stefansson, Kari; Stefansson, Hreinn; Thornorgeirsson, Thornorgeir; Steinberg, Stacy; Gustafsson, Omar; 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; Sigur Sson, Engilbert; Müller-Mysok, Bertram; Lucae, Susanne; Schwarz, Markus; Schofield, Peter R; Martin, Nick; Montgomery, Grant W; Lathrop, Mark; Oskarsson, Högni; Bauer, Michael; Wright, Adam; Mitchell, Philip B; Hautzinger, Martin; Reif, Andreas; Kelsoe, John R; Purcell, Shaun M
Affiliation:
Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. pamela.sklar@mssm.edu
Citation:
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. 2011, 43 (10):977-83 Nat. Genet.
Journal:
Nature genetics
Issue Date:
Oct-2011
URI:
http://hdl.handle.net/10147/238795
DOI:
10.1038/ng.943
PubMed ID:
21926972
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.
Item Type:
Article
Language:
en
MeSH:
Alleles; Bipolar Disorder; Calcium Channels, L-Type; Case-Control Studies; Databases, Genetic; Genetic Loci; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Nuclear Proteins; Polymorphism, Single Nucleotide; Schizophrenia
ISSN:
1546-1718

Full metadata record

DC FieldValue Language
dc.contributor.authorSklar, Pamelaen_GB
dc.contributor.authorRipke, Stephanen_GB
dc.contributor.authorScott, Laura Jen_GB
dc.contributor.authorAndreassen, Ole Aen_GB
dc.contributor.authorCichon, Svenen_GB
dc.contributor.authorCraddock, Nicken_GB
dc.contributor.authorEdenberg, Howard Jen_GB
dc.contributor.authorNurnberger, John Ien_GB
dc.contributor.authorRietschel, Marcellaen_GB
dc.contributor.authorBlackwood, Douglasen_GB
dc.contributor.authorCorvin, Aidenen_GB
dc.contributor.authorFlickinger, Matthewen_GB
dc.contributor.authorGuan, Weihuaen_GB
dc.contributor.authorMattingsdal, Mortenen_GB
dc.contributor.authorMcQuillin, Andrewen_GB
dc.contributor.authorKwan, Phoenixen_GB
dc.contributor.authorWienker, Thomas Fen_GB
dc.contributor.authorDaly, Marken_GB
dc.contributor.authorDudbridge, Franken_GB
dc.contributor.authorHolmans, Peter Aen_GB
dc.contributor.authorLin, Danyuen_GB
dc.contributor.authorBurmeister, Margiten_GB
dc.contributor.authorGreenwood, Tiffany Aen_GB
dc.contributor.authorHamshere, Marian Len_GB
dc.contributor.authorMuglia, Pierandreaen_GB
dc.contributor.authorSmith, Erin Nen_GB
dc.contributor.authorZandi, Peter Pen_GB
dc.contributor.authorNievergelt, Caroline Men_GB
dc.contributor.authorMcKinney, Rebeccaen_GB
dc.contributor.authorShilling, Paul Den_GB
dc.contributor.authorSchork, Nicholas Jen_GB
dc.contributor.authorBloss, Cinnamon Sen_GB
dc.contributor.authorForoud, Tatianaen_GB
dc.contributor.authorKoller, Daniel Len_GB
dc.contributor.authorGershon, Elliot Sen_GB
dc.contributor.authorLiu, Chunyuen_GB
dc.contributor.authorBadner, Judith Aen_GB
dc.contributor.authorScheftner, William Aen_GB
dc.contributor.authorLawson, William Ben_GB
dc.contributor.authorNwulia, Evaristus Aen_GB
dc.contributor.authorHipolito, Mariaen_GB
dc.contributor.authorCoryell, Williamen_GB
dc.contributor.authorRice, Johnen_GB
dc.contributor.authorByerley, Williamen_GB
dc.contributor.authorMcMahon, Francis Jen_GB
dc.contributor.authorSchulze, Thomas Gen_GB
dc.contributor.authorBerrettini, Wadeen_GB
dc.contributor.authorLohoff, Falk Wen_GB
dc.contributor.authorPotash, James Ben_GB
dc.contributor.authorMahon, Pamela Ben_GB
dc.contributor.authorMcInnis, Melvin Gen_GB
dc.contributor.authorZöllner, Sebastianen_GB
dc.contributor.authorZhang, Pengen_GB
dc.contributor.authorCraig, David Wen_GB
dc.contributor.authorSzelinger, Szaboclsen_GB
dc.contributor.authorBarrett, Thomas Ben_GB
dc.contributor.authorBreuer, Renéen_GB
dc.contributor.authorMeier, Sandraen_GB
dc.contributor.authorStrohmaier, Janaen_GB
dc.contributor.authorWitt, Stephanie Hen_GB
dc.contributor.authorTozzi, Federicaen_GB
dc.contributor.authorFarmer, Anneen_GB
dc.contributor.authorMcGuffin, Peteren_GB
dc.contributor.authorStrauss, Johnen_GB
dc.contributor.authorXu, Weien_GB
dc.contributor.authorKennedy, James Len_GB
dc.contributor.authorVincent, John Ben_GB
dc.contributor.authorMatthews, Keithen_GB
dc.contributor.authorDay, Richarden_GB
dc.contributor.authorFerreira, Manuel Aen_GB
dc.contributor.authorO'Dushlaine, Colmen_GB
dc.contributor.authorPerlis, Royen_GB
dc.contributor.authorRaychaudhuri, Soumyaen_GB
dc.contributor.authorRuderfer, Douglasen_GB
dc.contributor.authorHyoun, Phil Len_GB
dc.contributor.authorSmoller, Jordan Wen_GB
dc.contributor.authorLi, Junen_GB
dc.contributor.authorAbsher, Devinen_GB
dc.contributor.authorThompson, Robert Cen_GB
dc.contributor.authorMeng, Fan Guoen_GB
dc.contributor.authorSchatzberg, Alan Fen_GB
dc.contributor.authorBunney, William Een_GB
dc.contributor.authorBarchas, Jack Den_GB
dc.contributor.authorJones, Edward Gen_GB
dc.contributor.authorWatson, Stanley Jen_GB
dc.contributor.authorMyers, Richard Men_GB
dc.contributor.authorAkil, Hudaen_GB
dc.contributor.authorBoehnke, Michaelen_GB
dc.contributor.authorChambert, Kimen_GB
dc.contributor.authorMoran, Jenniferen_GB
dc.contributor.authorScolnick, Eden_GB
dc.contributor.authorDjurovic, Srdjanen_GB
dc.contributor.authorMelle, Ingriden_GB
dc.contributor.authorMorken, Gunnaren_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorMorris, Dereken_GB
dc.contributor.authorQuinn, Emmaen_GB
dc.contributor.authorMühleisen, Thomas Wen_GB
dc.contributor.authorDegenhardt, Franziska Aen_GB
dc.contributor.authorMattheisen, Manuelen_GB
dc.contributor.authorSchumacher, Johannesen_GB
dc.contributor.authorMaier, Wolfgangen_GB
dc.contributor.authorSteffens, Michaelen_GB
dc.contributor.authorPropping, Peteren_GB
dc.contributor.authorNöthen, Markus Men_GB
dc.contributor.authorAnjorin, Adebayoen_GB
dc.contributor.authorBass, Nicken_GB
dc.contributor.authorGurling, Hughen_GB
dc.contributor.authorKandaswamy, Radhikaen_GB
dc.contributor.authorLawrence, Jacoben_GB
dc.contributor.authorMcGhee, Kevinen_GB
dc.contributor.authorMcIntosh, Andrewen_GB
dc.contributor.authorMcLean, Alan Wen_GB
dc.contributor.authorMuir, Walter Jen_GB
dc.contributor.authorPickard, Benjamin Sen_GB
dc.contributor.authorBreen, Geromeen_GB
dc.contributor.authorSt Clair, Daviden_GB
dc.contributor.authorCaesar, Sianen_GB
dc.contributor.authorGordon-Smith, Katherineen_GB
dc.contributor.authorJones, Lisaen_GB
dc.contributor.authorFraser, Christineen_GB
dc.contributor.authorGreen, Elaine Ken_GB
dc.contributor.authorGrozeva, Detelinaen_GB
dc.contributor.authorJones, Ian Ren_GB
dc.contributor.authorKirov, Georgeen_GB
dc.contributor.authorMoskvina, Valentinaen_GB
dc.contributor.authorNikolov, Ivanen_GB
dc.contributor.authorO'Donovan, Michael Cen_GB
dc.contributor.authorOwen, Michael Jen_GB
dc.contributor.authorCollier, David Aen_GB
dc.contributor.authorElkin, Amandaen_GB
dc.contributor.authorWilliamson, Richarden_GB
dc.contributor.authorYoung, Allan Hen_GB
dc.contributor.authorFerrier, I Nicolen_GB
dc.contributor.authorStefansson, Karien_GB
dc.contributor.authorStefansson, Hreinnen_GB
dc.contributor.authorThornorgeirsson, Thornorgeiren_GB
dc.contributor.authorSteinberg, Stacyen_GB
dc.contributor.authorGustafsson, Omaren_GB
dc.contributor.authorBergen, Sarah Een_GB
dc.contributor.authorNimgaonkar, Vishwajiten_GB
dc.contributor.authorHultman, Christinaen_GB
dc.contributor.authorLandén, Mikaelen_GB
dc.contributor.authorLichtenstein, Paulen_GB
dc.contributor.authorSullivan, Patricken_GB
dc.contributor.authorSchalling, Martinen_GB
dc.contributor.authorOsby, Urbanen_GB
dc.contributor.authorBacklund, Lenaen_GB
dc.contributor.authorFrisén, Louiseen_GB
dc.contributor.authorLangstrom, Niklasen_GB
dc.contributor.authorJamain, Stéphaneen_GB
dc.contributor.authorLeboyer, Marionen_GB
dc.contributor.authorEtain, Brunoen_GB
dc.contributor.authorBellivier, Franken_GB
dc.contributor.authorPetursson, Hannesen_GB
dc.contributor.authorSigur Sson, Engilberten_GB
dc.contributor.authorMüller-Mysok, Bertramen_GB
dc.contributor.authorLucae, Susanneen_GB
dc.contributor.authorSchwarz, Markusen_GB
dc.contributor.authorSchofield, Peter Ren_GB
dc.contributor.authorMartin, Nicken_GB
dc.contributor.authorMontgomery, Grant Wen_GB
dc.contributor.authorLathrop, Marken_GB
dc.contributor.authorOskarsson, Högnien_GB
dc.contributor.authorBauer, Michaelen_GB
dc.contributor.authorWright, Adamen_GB
dc.contributor.authorMitchell, Philip Ben_GB
dc.contributor.authorHautzinger, Martinen_GB
dc.contributor.authorReif, Andreasen_GB
dc.contributor.authorKelsoe, John Ren_GB
dc.contributor.authorPurcell, Shaun Men_GB
dc.date.accessioned2012-08-15T14:10:55Z-
dc.date.available2012-08-15T14:10:55Z-
dc.date.issued2011-10-
dc.identifier.citationLarge-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. 2011, 43 (10):977-83 Nat. Genet.en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid21926972-
dc.identifier.doi10.1038/ng.943-
dc.identifier.urihttp://hdl.handle.net/10147/238795-
dc.description.abstractWe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subject.meshAlleles-
dc.subject.meshBipolar Disorder-
dc.subject.meshCalcium Channels, L-Type-
dc.subject.meshCase-Control Studies-
dc.subject.meshDatabases, Genetic-
dc.subject.meshGenetic Loci-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome, Human-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshNuclear Proteins-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshSchizophrenia-
dc.titleLarge-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.en_GB
dc.typeArticleen
dc.contributor.departmentDivision of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. pamela.sklar@mssm.eduen_GB
dc.identifier.journalNature geneticsen_GB
dc.description.provinceLeinsteren

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