Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2

M. C. O'Donovan; N. Norton; H. Williams; T. Peirce; V. Moskvina; I. Nikolov; M. Hamshere; L. Carroll; L. Georgieva; S. Dwyer; P. Holmans; J. L. Marchini; C. C.A. Spencer; B. Howie; H. T. Leung; I. Giegling; A. M. Hartmann; H. J. Möller; D. W. Morris; Y. Shi; G. Feng; P. Hoffmann; P. Propping; C. Vasilescu; W. Maier; M. Rietschel; S. Zammit; J. Schumacher; E. M. Quinn; T. G. Schulze; N. Iwata; M. Ikeda; A. Darvasi; S. Shifman; L. He; J. Duan; A. R. Sanders; D. F. Levinson; R. Adolfsson; U. Ösby; L. Terenius; E. G. Jönsson; S. Cichon; M. M. Nöthen; M. Gill; A. P. Corvin; D. Rujescu; P. V. Gejman; G. Kirov; N. Craddock; N. M. Williams; M. J. Owen; P. V. Gejman; A. R. Sanders; J. Duan; D. F. Levinson; N. G. Buccola; B. J. Mowry; R. Freedman; F. Amin; D. W. Black; J. M. Silverman; W. J. Byerley; C. R. Cloninger

doi:10.1038/mp.2008.108

Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2

M. C. O'Donovan, N. Norton, H. Williams, T. Peirce, V. Moskvina, I. Nikolov, M. Hamshere, L. Carroll, L. Georgieva, S. Dwyer, P. Holmans, J. L. Marchini, C. C.A. Spencer, B. Howie, H. T. Leung, I. Giegling, A. M. Hartmann, H. J. Möller, D. W. Morris, Y. ShiG. Feng, P. Hoffmann, P. Propping, C. Vasilescu, W. Maier, M. Rietschel, S. Zammit, J. Schumacher, E. M. Quinn, T. G. Schulze, N. Iwata, M. Ikeda, A. Darvasi, S. Shifman, L. He, J. Duan, A. R. Sanders, D. F. Levinson, R. Adolfsson, U. Ösby, L. Terenius, E. G. Jönsson, S. Cichon, M. M. Nöthen, M. Gill, A. P. Corvin, D. Rujescu, P. V. Gejman, G. Kirov, N. Craddock, N. M. Williams, M. J. Owen, P. V. Gejman, A. R. Sanders, J. Duan, D. F. Levinson, N. G. Buccola, B. J. Mowry, R. Freedman, F. Amin, D. W. Black, J. M. Silverman, W. J. Byerley, C. R. Cloninger

Department of Genetics

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59 Scopus citations

Abstract

We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

Original language	English
Pages (from-to)	30-36
Number of pages	7
Journal	Molecular Psychiatry
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/mp.2008.108
State	Published - 25 Jan 2009

Bibliographical note

Funding Information:
This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The UK research was supported by grants from the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50 MH066392-05A1. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland), and the Wellcome Trust. We are grateful to Professor John Waddington for sample recruitment. Irish controls were supplied by Dr Joe McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the ‘Bundesminister-ium für Bildung und Forschung’ (BMBF), the Alfried Krupp von Bohlen und Halbach-Stiftung and in Bethesda the work was supported in part by the Intramural Program of the NIMH. We also thank the Department of Psychiatry, LMU Munich for clinical characterization of the Munich subjects and the processing of the samples. Recruitment in Munich was partially supported by GlaxoSmithKline. The Ashkenazi samples are part of the Hebrew University Genetic Resource, HUGR (www.hugr.org). In Sweden support was obtained from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3), the Wallenberg Foundation and the HUBIN project. The following authors are included under the Molecular Genetics of Schizophrenia Collaboration: PV Gejman, AR Sanders, J Duan (Evanston Healthcare and Northwestern University, IL, USA), DF Levinson (Stanford University, CA, USA), NG Buccola (Louisiana State University, LA, USA), BJ Mowry (University of Queensland, Brisbane, Australia), R Freedman (University of Colorado Health Science Centre, Denver, USA), F Amin (Emory University, Atlanta, USA), DW Black (University of Iowa College of Medicine, IA, USA), JM Silverman (Mount Sinai School of Medicine, New York, USA), WJ Byerley (University of California, San Francisco, USA), CR Cloninger (Washington University).

Keywords

FGFR2
Genome-wide association study
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/mp.2008.108

Cite this

O'Donovan, M. C., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., Georgieva, L., Dwyer, S., Holmans, P., Marchini, J. L., Spencer, C. C. A., Howie, B., Leung, H. T., Giegling, I., Hartmann, A. M., Möller, H. J., Morris, D. W., ... Cloninger, C. R. (2009). Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. Molecular Psychiatry, 14(1), 30-36. https://doi.org/10.1038/mp.2008.108

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title = "Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2",

abstract = "We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.",

keywords = "FGFR2, Genome-wide association study, Schizophrenia",

author = "O'Donovan, {M. C.} and N. Norton and H. Williams and T. Peirce and V. Moskvina and I. Nikolov and M. Hamshere and L. Carroll and L. Georgieva and S. Dwyer and P. Holmans and Marchini, {J. L.} and Spencer, {C. C.A.} and B. Howie and Leung, {H. T.} and I. Giegling and Hartmann, {A. M.} and M{\"o}ller, {H. J.} and Morris, {D. W.} and Y. Shi and G. Feng and P. Hoffmann and P. Propping and C. Vasilescu and W. Maier and M. Rietschel and S. Zammit and J. Schumacher and Quinn, {E. M.} and Schulze, {T. G.} and N. Iwata and M. Ikeda and A. Darvasi and S. Shifman and L. He and J. Duan and Sanders, {A. R.} and Levinson, {D. F.} and R. Adolfsson and U. {\"O}sby and L. Terenius and J{\"o}nsson, {E. G.} and S. Cichon and N{\"o}then, {M. M.} and M. Gill and Corvin, {A. P.} and D. Rujescu and Gejman, {P. V.} and G. Kirov and N. Craddock and Williams, {N. M.} and Owen, {M. J.} and Gejman, {P. V.} and Sanders, {A. R.} and J. Duan and Levinson, {D. F.} and Buccola, {N. G.} and Mowry, {B. J.} and R. Freedman and F. Amin and Black, {D. W.} and Silverman, {J. M.} and Byerley, {W. J.} and Cloninger, {C. R.}",

note = "Funding Information: This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The UK research was supported by grants from the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50 MH066392-05A1. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland), and the Wellcome Trust. We are grateful to Professor John Waddington for sample recruitment. Irish controls were supplied by Dr Joe McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the {\textquoteleft}Bundesminister-ium f{\"u}r Bildung und Forschung{\textquoteright} (BMBF), the Alfried Krupp von Bohlen und Halbach-Stiftung and in Bethesda the work was supported in part by the Intramural Program of the NIMH. We also thank the Department of Psychiatry, LMU Munich for clinical characterization of the Munich subjects and the processing of the samples. Recruitment in Munich was partially supported by GlaxoSmithKline. The Ashkenazi samples are part of the Hebrew University Genetic Resource, HUGR (www.hugr.org). In Sweden support was obtained from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3), the Wallenberg Foundation and the HUBIN project. The following authors are included under the Molecular Genetics of Schizophrenia Collaboration: PV Gejman, AR Sanders, J Duan (Evanston Healthcare and Northwestern University, IL, USA), DF Levinson (Stanford University, CA, USA), NG Buccola (Louisiana State University, LA, USA), BJ Mowry (University of Queensland, Brisbane, Australia), R Freedman (University of Colorado Health Science Centre, Denver, USA), F Amin (Emory University, Atlanta, USA), DW Black (University of Iowa College of Medicine, IA, USA), JM Silverman (Mount Sinai School of Medicine, New York, USA), WJ Byerley (University of California, San Francisco, USA), CR Cloninger (Washington University).",

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O'Donovan, MC, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L, Dwyer, S, Holmans, P, Marchini, JL, Spencer, CCA, Howie, B, Leung, HT, Giegling, I, Hartmann, AM, Möller, HJ, Morris, DW, Shi, Y, Feng, G, Hoffmann, P, Propping, P, Vasilescu, C, Maier, W, Rietschel, M, Zammit, S, Schumacher, J, Quinn, EM, Schulze, TG, Iwata, N, Ikeda, M, Darvasi, A, Shifman, S, He, L, Duan, J, Sanders, AR, Levinson, DF, Adolfsson, R, Ösby, U, Terenius, L, Jönsson, EG, Cichon, S, Nöthen, MM, Gill, M, Corvin, AP, Rujescu, D, Gejman, PV, Kirov, G, Craddock, N, Williams, NM, Owen, MJ, Gejman, PV, Sanders, AR, Duan, J, Levinson, DF, Buccola, NG, Mowry, BJ, Freedman, R, Amin, F, Black, DW, Silverman, JM, Byerley, WJ & Cloninger, CR 2009, 'Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2', Molecular Psychiatry, vol. 14, no. 1, pp. 30-36. https://doi.org/10.1038/mp.2008.108

TY - JOUR

T1 - Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2

AU - O'Donovan, M. C.

AU - Norton, N.

AU - Williams, H.

AU - Peirce, T.

AU - Moskvina, V.

AU - Nikolov, I.

AU - Hamshere, M.

AU - Carroll, L.

AU - Georgieva, L.

AU - Dwyer, S.

AU - Holmans, P.

AU - Marchini, J. L.

AU - Spencer, C. C.A.

AU - Howie, B.

AU - Leung, H. T.

AU - Giegling, I.

AU - Hartmann, A. M.

AU - Möller, H. J.

AU - Morris, D. W.

AU - Shi, Y.

AU - Feng, G.

AU - Hoffmann, P.

AU - Propping, P.

AU - Vasilescu, C.

AU - Maier, W.

AU - Rietschel, M.

AU - Zammit, S.

AU - Schumacher, J.

AU - Quinn, E. M.

AU - Schulze, T. G.

AU - Iwata, N.

AU - Ikeda, M.

AU - Darvasi, A.

AU - Shifman, S.

AU - He, L.

AU - Duan, J.

AU - Sanders, A. R.

AU - Levinson, D. F.

AU - Adolfsson, R.

AU - Ösby, U.

AU - Terenius, L.

AU - Jönsson, E. G.

AU - Cichon, S.

AU - Nöthen, M. M.

AU - Gill, M.

AU - Corvin, A. P.

AU - Rujescu, D.

AU - Gejman, P. V.

AU - Kirov, G.

AU - Craddock, N.

AU - Williams, N. M.

AU - Owen, M. J.

AU - Gejman, P. V.

AU - Sanders, A. R.

AU - Duan, J.

AU - Levinson, D. F.

AU - Buccola, N. G.

AU - Mowry, B. J.

AU - Freedman, R.

AU - Amin, F.

AU - Black, D. W.

AU - Silverman, J. M.

AU - Byerley, W. J.

AU - Cloninger, C. R.

N1 - Funding Information: This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The UK research was supported by grants from the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50 MH066392-05A1. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland), and the Wellcome Trust. We are grateful to Professor John Waddington for sample recruitment. Irish controls were supplied by Dr Joe McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the ‘Bundesminister-ium für Bildung und Forschung’ (BMBF), the Alfried Krupp von Bohlen und Halbach-Stiftung and in Bethesda the work was supported in part by the Intramural Program of the NIMH. We also thank the Department of Psychiatry, LMU Munich for clinical characterization of the Munich subjects and the processing of the samples. Recruitment in Munich was partially supported by GlaxoSmithKline. The Ashkenazi samples are part of the Hebrew University Genetic Resource, HUGR (www.hugr.org). In Sweden support was obtained from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3), the Wallenberg Foundation and the HUBIN project. The following authors are included under the Molecular Genetics of Schizophrenia Collaboration: PV Gejman, AR Sanders, J Duan (Evanston Healthcare and Northwestern University, IL, USA), DF Levinson (Stanford University, CA, USA), NG Buccola (Louisiana State University, LA, USA), BJ Mowry (University of Queensland, Brisbane, Australia), R Freedman (University of Colorado Health Science Centre, Denver, USA), F Amin (Emory University, Atlanta, USA), DW Black (University of Iowa College of Medicine, IA, USA), JM Silverman (Mount Sinai School of Medicine, New York, USA), WJ Byerley (University of California, San Francisco, USA), CR Cloninger (Washington University).

PY - 2009/1/25

Y1 - 2009/1/25

N2 - We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

AB - We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

KW - FGFR2

KW - Genome-wide association study

KW - Schizophrenia

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Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2

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Bibliographical note

Keywords

UN SDGs

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