Genome-wide association study identifies five new schizophrenia loci
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium reports five genetic loci newly associated with risk of schizophrenia, involving 17,836 cases of schizophrenia and 33,859 healthy controls. The new locus with the strongest support of association was located within an intron for...
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| Published in | Nature genetics Vol. 43; no. 10; pp. 969 - 976 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.10.2011
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The Schizophrenia Psychiatric Genome-Wide Association Study Consortium reports five genetic loci newly associated with risk of schizophrenia, involving 17,836 cases of schizophrenia and 33,859 healthy controls. The new locus with the strongest support of association was located within an intron for microRNA 137, a known regulator of neuronal development. Four other genome-wide significant loci for schizophrenia contain predicted targets of
MIR137
, suggesting that disruption to pathways involving
MIR137
may be an etiologic mechanism in schizophrenia.
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
). |
|---|---|
| AbstractList | 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)). 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 ). 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 (1 p21.3, 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 x [10.sup.-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 MIR/37-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 x [10.sup.-9]), ANK3 (rs10994359, P = 2.5 x [10.sup.-8]) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x [10.sup.-9]). 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)).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)). 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^sup -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^sup -9^), ANK3 (rs10994359, P = 2.5 × 10^sup -8^) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10^sup -9^). [PUBLICATION 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 x 10 super(-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 x 10 super(-9)), ANK3 (rs10994359, P = 2.5 x 10 super(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10 super(-9)). The Schizophrenia Psychiatric Genome-Wide Association Study Consortium reports five genetic loci newly associated with risk of schizophrenia, involving 17,836 cases of schizophrenia and 33,859 healthy controls. The new locus with the strongest support of association was located within an intron for microRNA 137, a known regulator of neuronal development. Four other genome-wide significant loci for schizophrenia contain predicted targets of MIR137 , suggesting that disruption to pathways involving MIR137 may be an etiologic mechanism in schizophrenia. 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 ). |
| Audience | Academic |
| Author | Duan, Jubao Holmans, Peter A Purcell, Shaun Lin, Dan-Yu Posthuma, Danielle Pietilaeinen, Olli P H Gurling, Hugh Bitter, Istvan St Clair, David Amdur, Richard L De Hert, Marc Visscher, Peter M Ruderfer, Douglas M Pato, Carlos N Albus, Margot Alexander, Madeline Jonsson, Erik G Sanders, Alan R Blackwood, Douglas H R Ophoff, Roel A Tosato, Sarah Boerglum, Anders D Levinson, Douglas F Sklar, Pamela Neale, Benjamin M Black, Donald W Andreassen, Ole A Golimbet, Vera Collier, David A Bergen, Sarah E Ripke, Stephan Steinberg, Stacy Bruggeman, Richard Kendler, Kenneth S Agartz, Ingrid Amin, Farooq Cichon, Sven Dudbridge, Frank Buccola, Nancy G Malhotra, Anil K Bass, Nicholas Scolnick, Edward Corvin, Aiden Brown, Matthew A Mowry, Bryan J Werge, Thomas Stefansson, Hreinn Fanous, Ayman Rujescu, Dan Rossin, Lizzy |
| AuthorAffiliation | Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA |
| AuthorAffiliation_xml | – name: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA |
| Author_xml | – sequence: 1 givenname: Stephan surname: Ripke fullname: Ripke, Stephan – sequence: 2 givenname: Alan surname: Sanders middlename: R fullname: Sanders, Alan R – sequence: 3 givenname: Kenneth surname: Kendler middlename: S fullname: Kendler, Kenneth S – sequence: 4 givenname: Douglas surname: Levinson middlename: F fullname: Levinson, Douglas F – sequence: 5 givenname: Pamela surname: Sklar fullname: Sklar, Pamela – sequence: 6 givenname: Peter surname: Holmans middlename: A fullname: Holmans, Peter A – sequence: 7 givenname: Dan-Yu surname: Lin fullname: Lin, Dan-Yu – sequence: 8 givenname: Jubao surname: Duan fullname: Duan, Jubao – sequence: 9 givenname: Roel surname: Ophoff middlename: A fullname: Ophoff, Roel A – sequence: 10 givenname: Ole surname: Andreassen middlename: A fullname: Andreassen, Ole A – sequence: 11 givenname: Edward surname: Scolnick fullname: Scolnick, Edward – sequence: 12 givenname: Sven surname: Cichon fullname: Cichon, Sven – sequence: 13 givenname: David surname: St Clair fullname: St Clair, David – sequence: 14 givenname: Aiden surname: Corvin fullname: Corvin, Aiden – sequence: 15 givenname: Hugh surname: Gurling fullname: Gurling, Hugh – sequence: 16 givenname: Thomas surname: Werge fullname: Werge, Thomas – sequence: 17 givenname: Dan surname: Rujescu fullname: Rujescu, Dan – sequence: 18 givenname: Douglas surname: Blackwood middlename: H R fullname: Blackwood, Douglas H R – sequence: 19 givenname: Carlos surname: Pato middlename: N fullname: Pato, Carlos N – sequence: 20 givenname: Anil surname: Malhotra middlename: K fullname: Malhotra, Anil K – sequence: 21 givenname: Shaun surname: Purcell fullname: Purcell, Shaun – sequence: 22 givenname: Frank surname: Dudbridge fullname: Dudbridge, Frank – sequence: 23 givenname: Benjamin surname: Neale middlename: M fullname: Neale, Benjamin M – sequence: 24 givenname: Lizzy surname: Rossin fullname: Rossin, Lizzy – sequence: 25 givenname: Peter surname: Visscher middlename: M fullname: Visscher, Peter M – sequence: 26 givenname: Danielle surname: Posthuma fullname: Posthuma, Danielle – sequence: 27 givenname: Douglas surname: Ruderfer middlename: M fullname: Ruderfer, Douglas M – sequence: 28 givenname: Ayman surname: Fanous fullname: Fanous, Ayman – sequence: 29 givenname: Hreinn surname: Stefansson fullname: Stefansson, Hreinn – sequence: 30 givenname: Stacy surname: Steinberg fullname: Steinberg, Stacy – sequence: 31 givenname: Bryan surname: Mowry middlename: J fullname: Mowry, Bryan J – sequence: 32 givenname: Vera surname: Golimbet fullname: Golimbet, Vera – sequence: 33 givenname: Marc surname: De Hert fullname: De Hert, Marc – sequence: 34 givenname: Erik surname: Jonsson middlename: G fullname: Jonsson, Erik G – sequence: 35 givenname: Istvan surname: Bitter fullname: Bitter, Istvan – sequence: 36 givenname: Olli surname: Pietilaeinen middlename: P H fullname: Pietilaeinen, Olli P H – sequence: 37 givenname: David surname: Collier middlename: A fullname: Collier, David A – sequence: 38 givenname: Sarah surname: Tosato fullname: Tosato, Sarah – sequence: 39 givenname: Ingrid surname: Agartz fullname: Agartz, Ingrid – sequence: 40 givenname: Margot surname: Albus fullname: Albus, Margot – sequence: 41 givenname: Madeline surname: Alexander fullname: Alexander, Madeline – sequence: 42 givenname: Richard surname: Amdur middlename: L fullname: Amdur, Richard L – sequence: 43 givenname: Farooq surname: Amin fullname: Amin, Farooq – sequence: 44 givenname: Nicholas surname: Bass fullname: Bass, Nicholas – sequence: 45 givenname: Sarah surname: Bergen middlename: E fullname: Bergen, Sarah E – sequence: 46 givenname: Donald surname: Black middlename: W fullname: Black, Donald W – sequence: 47 givenname: Anders surname: Boerglum middlename: D fullname: Boerglum, Anders D – sequence: 48 givenname: Matthew surname: Brown middlename: A fullname: Brown, Matthew A – sequence: 49 givenname: Richard surname: Bruggeman fullname: Bruggeman, Richard – sequence: 50 givenname: Nancy surname: Buccola middlename: G fullname: Buccola, Nancy G |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24606816$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21926974$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:123309878$$DView record from Swedish Publication Index |
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| PublicationTitle | Nature genetics |
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| Snippet | The Schizophrenia Psychiatric Genome-Wide Association Study Consortium reports five genetic loci newly associated with risk of schizophrenia, involving 17,836... 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... |
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| SubjectTerms | 631/208/205/2138 631/208/2489/144 692/699/476/1333 692/699/476/1799 Adult and adolescent clinical studies Agriculture Alleles Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Bipolar Disorder Cancer Research Case-Control Studies Female Fundamental and applied biological sciences. Psychology Gene Dosage Gene Expression Regulation Gene Function Genealogy Genetic aspects Genetic diversity Genetic Loci Genetic Predisposition to Disease Genetic variation Genetics of eukaryotes. Biological and molecular evolution Genome, Human Genome-Wide Association Study Genomes Haplotypes Human Genetics Humans letter Linkage Disequilibrium Logistic Models Male Medical sciences Mental disorders MicroRNA MicroRNAs - genetics MicroRNAs - metabolism Mutation Physiological aspects Polymorphism, Single Nucleotide Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Risk factors Schizophrenia Schizophrenia - genetics Studies White People |
| Title | Genome-wide association study identifies five new schizophrenia loci |
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