Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 by Psychiatric GWAS Consortium Bipolar Disorder Working Group, 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 in Nature genetics (2011). PubMed

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.

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