Genome-wide association study identifies five new schizophrenia loci.

Hdl Handle:
http://hdl.handle.net/10147/238794
Title:
Genome-wide association study identifies five new schizophrenia loci.
Authors:
Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S; Levinson, Douglas F; Sklar, Pamela; Holmans, Peter A; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A; Andreassen, Ole A; Scolnick, Edward; Cichon, Sven; St Clair, David; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H R; Pato, Carlos N; Malhotra, Anil K; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M; Rossin, Lizzy; Visscher, Peter M; Posthuma, Danielle; Ruderfer, Douglas M; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J; Golimbet, Vera; De Hert, Marc; Jönsson, Erik G; Bitter, István; Pietiläinen, Olli P H; Collier, David A; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E; Black, Donald W; Børglum, Anders D; Brown, Matthew A; Bruggeman, Richard; Buccola, Nancy G; Byerley, William F; Cahn, Wiepke; Cantor, Rita M; Carr, Vaughan J; Catts, Stanley V; Choudhury, Khalid; Cloninger, C Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A; Datta, Susmita; de Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthøj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M; Henskens, Frans A; Hougaard, David M; Hultman, Christina M; Ingason, Andrés; Jablensky, Assen V; Jakobsen, Klaus D; Jay, Maurice; Jürgens, Gesche; Kahn, René S; Keller, Matthew C; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A; Linszen, Don H; Lönnqvist, Jouko; Loughland, Carmel M; Maclean, Alan W; Maher, Brion S; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A; McGrath, John J; McIntosh, Andrew; McLean, Duncan E; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T; Milanova, Vihra; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Nöthen, Markus M; O'Dushlaine, Colm T; Olincy, Ann; Olsen, Line; O'Neill, F Anthony; Orntoft, Torben F; Owen, Michael J; Pantelis, Christos; Papadimitriou, George; Pato, Michele T; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E; Puri, Vinay; Quested, Digby; Quinn, Emma M; Rasmussen, Henrik B; Réthelyi, János M; Ribble, Robert; Rietschel, Marcella; Riley, Brien P; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G; Schwab, Sibylle G; Scott, Rodney J; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M; Spencer, Chris C A; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G; Wiersma, Durk; Wildenauer, Dieter B; Williams, Hywel J; Williams, Nigel M; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F; O'Donovan, Michael C; Daly, Mark J; Gejman, Pablo V
Affiliation:
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
Citation:
Genome-wide association study identifies five new schizophrenia loci. 2011, 43 (10):969-76 Nat. Genet.
Journal:
Nature genetics
Issue Date:
Oct-2011
URI:
http://hdl.handle.net/10147/238794
DOI:
10.1038/ng.940
PubMed ID:
21926974
Abstract:
We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).
Item Type:
Article
Language:
en
MeSH:
Alleles; Bipolar Disorder; Case-Control Studies; European Continental Ancestry Group; Female; Gene Dosage; Gene Expression Regulation; Genetic Loci; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Haplotypes; Humans; Linkage Disequilibrium; Logistic Models; Male; MicroRNAs; Mutation; Polymorphism, Single Nucleotide; Schizophrenia
ISSN:
1546-1718

Full metadata record

DC FieldValue Language
dc.contributor.authorRipke, Stephanen_GB
dc.contributor.authorSanders, Alan Ren_GB
dc.contributor.authorKendler, Kenneth Sen_GB
dc.contributor.authorLevinson, Douglas Fen_GB
dc.contributor.authorSklar, Pamelaen_GB
dc.contributor.authorHolmans, Peter Aen_GB
dc.contributor.authorLin, Dan-Yuen_GB
dc.contributor.authorDuan, Jubaoen_GB
dc.contributor.authorOphoff, Roel Aen_GB
dc.contributor.authorAndreassen, Ole Aen_GB
dc.contributor.authorScolnick, Edwarden_GB
dc.contributor.authorCichon, Svenen_GB
dc.contributor.authorSt Clair, Daviden_GB
dc.contributor.authorCorvin, Aidenen_GB
dc.contributor.authorGurling, Hughen_GB
dc.contributor.authorWerge, Thomasen_GB
dc.contributor.authorRujescu, Danen_GB
dc.contributor.authorBlackwood, Douglas H Ren_GB
dc.contributor.authorPato, Carlos Nen_GB
dc.contributor.authorMalhotra, Anil Ken_GB
dc.contributor.authorPurcell, Shaunen_GB
dc.contributor.authorDudbridge, Franken_GB
dc.contributor.authorNeale, Benjamin Men_GB
dc.contributor.authorRossin, Lizzyen_GB
dc.contributor.authorVisscher, Peter Men_GB
dc.contributor.authorPosthuma, Danielleen_GB
dc.contributor.authorRuderfer, Douglas Men_GB
dc.contributor.authorFanous, Aymanen_GB
dc.contributor.authorStefansson, Hreinnen_GB
dc.contributor.authorSteinberg, Stacyen_GB
dc.contributor.authorMowry, Bryan Jen_GB
dc.contributor.authorGolimbet, Veraen_GB
dc.contributor.authorDe Hert, Marcen_GB
dc.contributor.authorJönsson, Erik Gen_GB
dc.contributor.authorBitter, Istvánen_GB
dc.contributor.authorPietiläinen, Olli P Hen_GB
dc.contributor.authorCollier, David Aen_GB
dc.contributor.authorTosato, Sarahen_GB
dc.contributor.authorAgartz, Ingriden_GB
dc.contributor.authorAlbus, Margoten_GB
dc.contributor.authorAlexander, Madelineen_GB
dc.contributor.authorAmdur, Richard Len_GB
dc.contributor.authorAmin, Farooqen_GB
dc.contributor.authorBass, Nicholasen_GB
dc.contributor.authorBergen, Sarah Een_GB
dc.contributor.authorBlack, Donald Wen_GB
dc.contributor.authorBørglum, Anders Den_GB
dc.contributor.authorBrown, Matthew Aen_GB
dc.contributor.authorBruggeman, Richarden_GB
dc.contributor.authorBuccola, Nancy Gen_GB
dc.contributor.authorByerley, William Fen_GB
dc.contributor.authorCahn, Wiepkeen_GB
dc.contributor.authorCantor, Rita Men_GB
dc.contributor.authorCarr, Vaughan Jen_GB
dc.contributor.authorCatts, Stanley Ven_GB
dc.contributor.authorChoudhury, Khaliden_GB
dc.contributor.authorCloninger, C Roberten_GB
dc.contributor.authorCormican, Paulen_GB
dc.contributor.authorCraddock, Nicholasen_GB
dc.contributor.authorDanoy, Patrick Aen_GB
dc.contributor.authorDatta, Susmitaen_GB
dc.contributor.authorde Haan, Lieuween_GB
dc.contributor.authorDemontis, Ditteen_GB
dc.contributor.authorDikeos, Dimitrisen_GB
dc.contributor.authorDjurovic, Srdjanen_GB
dc.contributor.authorDonnelly, Peteren_GB
dc.contributor.authorDonohoe, Garyen_GB
dc.contributor.authorDuong, Linhen_GB
dc.contributor.authorDwyer, Sarahen_GB
dc.contributor.authorFink-Jensen, Andersen_GB
dc.contributor.authorFreedman, Roberten_GB
dc.contributor.authorFreimer, Nelson Ben_GB
dc.contributor.authorFriedl, Marionen_GB
dc.contributor.authorGeorgieva, Lyudmilaen_GB
dc.contributor.authorGiegling, Inaen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorGlenthøj, Birteen_GB
dc.contributor.authorGodard, Stephanieen_GB
dc.contributor.authorHamshere, Marianen_GB
dc.contributor.authorHansen, Marken_GB
dc.contributor.authorHansen, Thomasen_GB
dc.contributor.authorHartmann, Annette Men_GB
dc.contributor.authorHenskens, Frans Aen_GB
dc.contributor.authorHougaard, David Men_GB
dc.contributor.authorHultman, Christina Men_GB
dc.contributor.authorIngason, Andrésen_GB
dc.contributor.authorJablensky, Assen Ven_GB
dc.contributor.authorJakobsen, Klaus Den_GB
dc.contributor.authorJay, Mauriceen_GB
dc.contributor.authorJürgens, Gescheen_GB
dc.contributor.authorKahn, René Sen_GB
dc.contributor.authorKeller, Matthew Cen_GB
dc.contributor.authorKenis, Gunteren_GB
dc.contributor.authorKenny, Elaineen_GB
dc.contributor.authorKim, Yunjungen_GB
dc.contributor.authorKirov, George Ken_GB
dc.contributor.authorKonnerth, Heikeen_GB
dc.contributor.authorKonte, Bettinaen_GB
dc.contributor.authorKrabbendam, Lydiaen_GB
dc.contributor.authorKrasucki, Roberten_GB
dc.contributor.authorLasseter, Virginia Ken_GB
dc.contributor.authorLaurent, Claudineen_GB
dc.contributor.authorLawrence, Jacoben_GB
dc.contributor.authorLencz, Todden_GB
dc.contributor.authorLerer, F Bernarden_GB
dc.contributor.authorLiang, Kung-Yeeen_GB
dc.contributor.authorLichtenstein, Paulen_GB
dc.contributor.authorLieberman, Jeffrey Aen_GB
dc.contributor.authorLinszen, Don Hen_GB
dc.contributor.authorLönnqvist, Joukoen_GB
dc.contributor.authorLoughland, Carmel Men_GB
dc.contributor.authorMaclean, Alan Wen_GB
dc.contributor.authorMaher, Brion Sen_GB
dc.contributor.authorMaier, Wolfgangen_GB
dc.contributor.authorMallet, Jacquesen_GB
dc.contributor.authorMalloy, Paten_GB
dc.contributor.authorMattheisen, Manuelen_GB
dc.contributor.authorMattingsdal, Mortenen_GB
dc.contributor.authorMcGhee, Kevin Aen_GB
dc.contributor.authorMcGrath, John Jen_GB
dc.contributor.authorMcIntosh, Andrewen_GB
dc.contributor.authorMcLean, Duncan Een_GB
dc.contributor.authorMcQuillin, Andrewen_GB
dc.contributor.authorMelle, Ingriden_GB
dc.contributor.authorMichie, Patricia Ten_GB
dc.contributor.authorMilanova, Vihraen_GB
dc.contributor.authorMorris, Derek Wen_GB
dc.contributor.authorMors, Oleen_GB
dc.contributor.authorMortensen, Preben Ben_GB
dc.contributor.authorMoskvina, Valentinaen_GB
dc.contributor.authorMuglia, Pierandreaen_GB
dc.contributor.authorMyin-Germeys, Inezen_GB
dc.contributor.authorNertney, Deborah Aen_GB
dc.contributor.authorNestadt, Geralden_GB
dc.contributor.authorNielsen, Jimmien_GB
dc.contributor.authorNikolov, Ivanen_GB
dc.contributor.authorNordentoft, Mereteen_GB
dc.contributor.authorNorton, Nadineen_GB
dc.contributor.authorNöthen, Markus Men_GB
dc.contributor.authorO'Dushlaine, Colm Ten_GB
dc.contributor.authorOlincy, Annen_GB
dc.contributor.authorOlsen, Lineen_GB
dc.contributor.authorO'Neill, F Anthonyen_GB
dc.contributor.authorOrntoft, Torben Fen_GB
dc.contributor.authorOwen, Michael Jen_GB
dc.contributor.authorPantelis, Christosen_GB
dc.contributor.authorPapadimitriou, Georgeen_GB
dc.contributor.authorPato, Michele Ten_GB
dc.contributor.authorPeltonen, Leenaen_GB
dc.contributor.authorPetursson, Hannesen_GB
dc.contributor.authorPickard, Benen_GB
dc.contributor.authorPimm, Jonathanen_GB
dc.contributor.authorPulver, Ann Een_GB
dc.contributor.authorPuri, Vinayen_GB
dc.contributor.authorQuested, Digbyen_GB
dc.contributor.authorQuinn, Emma Men_GB
dc.contributor.authorRasmussen, Henrik Ben_GB
dc.contributor.authorRéthelyi, János Men_GB
dc.contributor.authorRibble, Roberten_GB
dc.contributor.authorRietschel, Marcellaen_GB
dc.contributor.authorRiley, Brien Pen_GB
dc.contributor.authorRuggeri, Mirellaen_GB
dc.contributor.authorSchall, Ulrichen_GB
dc.contributor.authorSchulze, Thomas Gen_GB
dc.contributor.authorSchwab, Sibylle Gen_GB
dc.contributor.authorScott, Rodney Jen_GB
dc.contributor.authorShi, Jianxinen_GB
dc.contributor.authorSigurdsson, Engilberten_GB
dc.contributor.authorSilverman, Jeremy Men_GB
dc.contributor.authorSpencer, Chris C Aen_GB
dc.contributor.authorStefansson, Karien_GB
dc.contributor.authorStrange, Amyen_GB
dc.contributor.authorStrengman, Ericen_GB
dc.contributor.authorStroup, T Scotten_GB
dc.contributor.authorSuvisaari, Jaanaen_GB
dc.contributor.authorTerenius, Larsen_GB
dc.contributor.authorThirumalai, Srinivasaen_GB
dc.contributor.authorThygesen, Johan Hen_GB
dc.contributor.authorTimm, Sallyen_GB
dc.contributor.authorToncheva, Dragaen_GB
dc.contributor.authorvan den Oord, Edwinen_GB
dc.contributor.authorvan Os, Jimen_GB
dc.contributor.authorvan Winkel, Ruuden_GB
dc.contributor.authorVeldink, Janen_GB
dc.contributor.authorWalsh, Dermoten_GB
dc.contributor.authorWang, August Gen_GB
dc.contributor.authorWiersma, Durken_GB
dc.contributor.authorWildenauer, Dieter Ben_GB
dc.contributor.authorWilliams, Hywel Jen_GB
dc.contributor.authorWilliams, Nigel Men_GB
dc.contributor.authorWormley, Brandonen_GB
dc.contributor.authorZammit, Stanen_GB
dc.contributor.authorSullivan, Patrick Fen_GB
dc.contributor.authorO'Donovan, Michael Cen_GB
dc.contributor.authorDaly, Mark Jen_GB
dc.contributor.authorGejman, Pablo Ven_GB
dc.date.accessioned2012-08-15T14:10:02Z-
dc.date.available2012-08-15T14:10:02Z-
dc.date.issued2011-10-
dc.identifier.citationGenome-wide association study identifies five new schizophrenia loci. 2011, 43 (10):969-76 Nat. Genet.en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid21926974-
dc.identifier.doi10.1038/ng.940-
dc.identifier.urihttp://hdl.handle.net/10147/238794-
dc.description.abstractWe examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subject.meshAlleles-
dc.subject.meshBipolar Disorder-
dc.subject.meshCase-Control Studies-
dc.subject.meshEuropean Continental Ancestry Group-
dc.subject.meshFemale-
dc.subject.meshGene Dosage-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGenetic Loci-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome, Human-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHaplotypes-
dc.subject.meshHumans-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshLogistic Models-
dc.subject.meshMale-
dc.subject.meshMicroRNAs-
dc.subject.meshMutation-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshSchizophrenia-
dc.titleGenome-wide association study identifies five new schizophrenia loci.en_GB
dc.typeArticleen
dc.contributor.departmentCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.en_GB
dc.identifier.journalNature geneticsen_GB
dc.description.provinceLeinsteren

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.