GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.

Hdl Handle:
http://hdl.handle.net/10147/238806
Title:
GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.
Authors:
Chen, X; Lee, G; Maher, B S; Fanous, A H; Chen, J; Zhao, Z; Guo, A; van den Oord, E; Sullivan, P F; Shi, J; Levinson, D F; Gejman, P V; Sanders, A; Duan, J; Owen, M J; Craddock, N J; O'Donovan, M C; Blackman, J; Lewis, D; Kirov, G K; Qin, W; Schwab, S; Wildenauer, D; Chowdari, K; Nimgaonkar, V; Straub, R E; Weinberger, D R; O'Neill, F A; Walsh, D; Bronstein, M; Darvasi, A; Lencz, T; Malhotra, A K; Rujescu, D; Giegling, I; Werge, T; Hansen, T; Ingason, A; Nöethen, M M; Rietschel, M; Cichon, S; Djurovic, S; Andreassen, O A; Cantor, R M; Ophoff, R; Corvin, A; Morris, D W; Gill, M; Pato, C N; Pato, M T; Macedo, A; Gurling, H M D; McQuillin, A; Pimm, J; Hultman, C; Lichtenstein, P; Sklar, P; Purcell, S M; Scolnick, E; St Clair, D; Blackwood, D H R; Kendler, K S
Affiliation:
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0424, USA. xchen@vcu.edu
Citation:
GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia. 2011, 16 (11):1117-29 Mol. Psychiatry
Journal:
Molecular psychiatry
Issue Date:
Nov-2011
URI:
http://hdl.handle.net/10147/238806
DOI:
10.1038/mp.2010.96
PubMed ID:
20838396
Abstract:
We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.
Item Type:
Article
Language:
en
MeSH:
African Americans; Carrier Proteins; Case-Control Studies; Data Mining; European Continental Ancestry Group; Genome-Wide Association Study; Germany; Humans; Ireland; Jews; Linkage Disequilibrium; Muscle Proteins; Pennsylvania; Polymorphism, Single Nucleotide; Risk; Schizophrenia
ISSN:
1476-5578

Full metadata record

DC FieldValue Language
dc.contributor.authorChen, Xen_GB
dc.contributor.authorLee, Gen_GB
dc.contributor.authorMaher, B Sen_GB
dc.contributor.authorFanous, A Hen_GB
dc.contributor.authorChen, Jen_GB
dc.contributor.authorZhao, Zen_GB
dc.contributor.authorGuo, Aen_GB
dc.contributor.authorvan den Oord, Een_GB
dc.contributor.authorSullivan, P Fen_GB
dc.contributor.authorShi, Jen_GB
dc.contributor.authorLevinson, D Fen_GB
dc.contributor.authorGejman, P Ven_GB
dc.contributor.authorSanders, Aen_GB
dc.contributor.authorDuan, Jen_GB
dc.contributor.authorOwen, M Jen_GB
dc.contributor.authorCraddock, N Jen_GB
dc.contributor.authorO'Donovan, M Cen_GB
dc.contributor.authorBlackman, Jen_GB
dc.contributor.authorLewis, Den_GB
dc.contributor.authorKirov, G Ken_GB
dc.contributor.authorQin, Wen_GB
dc.contributor.authorSchwab, Sen_GB
dc.contributor.authorWildenauer, Den_GB
dc.contributor.authorChowdari, Ken_GB
dc.contributor.authorNimgaonkar, Ven_GB
dc.contributor.authorStraub, R Een_GB
dc.contributor.authorWeinberger, D Ren_GB
dc.contributor.authorO'Neill, F Aen_GB
dc.contributor.authorWalsh, Den_GB
dc.contributor.authorBronstein, Men_GB
dc.contributor.authorDarvasi, Aen_GB
dc.contributor.authorLencz, Ten_GB
dc.contributor.authorMalhotra, A Ken_GB
dc.contributor.authorRujescu, Den_GB
dc.contributor.authorGiegling, Ien_GB
dc.contributor.authorWerge, Ten_GB
dc.contributor.authorHansen, Ten_GB
dc.contributor.authorIngason, Aen_GB
dc.contributor.authorNöethen, M Men_GB
dc.contributor.authorRietschel, Men_GB
dc.contributor.authorCichon, Sen_GB
dc.contributor.authorDjurovic, Sen_GB
dc.contributor.authorAndreassen, O Aen_GB
dc.contributor.authorCantor, R Men_GB
dc.contributor.authorOphoff, Ren_GB
dc.contributor.authorCorvin, Aen_GB
dc.contributor.authorMorris, D Wen_GB
dc.contributor.authorGill, Men_GB
dc.contributor.authorPato, C Nen_GB
dc.contributor.authorPato, M Ten_GB
dc.contributor.authorMacedo, Aen_GB
dc.contributor.authorGurling, H M Den_GB
dc.contributor.authorMcQuillin, Aen_GB
dc.contributor.authorPimm, Jen_GB
dc.contributor.authorHultman, Cen_GB
dc.contributor.authorLichtenstein, Pen_GB
dc.contributor.authorSklar, Pen_GB
dc.contributor.authorPurcell, S Men_GB
dc.contributor.authorScolnick, Een_GB
dc.contributor.authorSt Clair, Den_GB
dc.contributor.authorBlackwood, D H Ren_GB
dc.contributor.authorKendler, K Sen_GB
dc.date.accessioned2012-08-15T14:24:51Z-
dc.date.available2012-08-15T14:24:51Z-
dc.date.issued2011-11-
dc.identifier.citationGWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia. 2011, 16 (11):1117-29 Mol. Psychiatryen_GB
dc.identifier.issn1476-5578-
dc.identifier.pmid20838396-
dc.identifier.doi10.1038/mp.2010.96-
dc.identifier.urihttp://hdl.handle.net/10147/238806-
dc.description.abstractWe conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Molecular psychiatryen_GB
dc.subject.meshAfrican Americans-
dc.subject.meshCarrier Proteins-
dc.subject.meshCase-Control Studies-
dc.subject.meshData Mining-
dc.subject.meshEuropean Continental Ancestry Group-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshGermany-
dc.subject.meshHumans-
dc.subject.meshIreland-
dc.subject.meshJews-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshMuscle Proteins-
dc.subject.meshPennsylvania-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshRisk-
dc.subject.meshSchizophrenia-
dc.titleGWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0424, USA. xchen@vcu.eduen_GB
dc.identifier.journalMolecular psychiatryen_GB
dc.description.provinceLeinsteren

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