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

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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 languageEnglish
Pages (from-to)30-36
Number of pages7
JournalMolecular Psychiatry
Volume14
Issue number1
DOIs
Publication statusPublished - 25-01-2009

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Receptor, Fibroblast Growth Factor, Type 2
Single Nucleotide Polymorphism
Schizophrenia
Genome-Wide Association Study
Germany
Nucleotide Mapping
Genes
Bulgaria
Israel
Ireland
Sweden
Meta-Analysis
China
Japan
Chromosomes
Alleles

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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. ; Shi, Y. ; Feng, G. ; Hoffmann, P. ; Propping, P. ; Vasilescu, C. ; Maier, W. ; Rietschel, M. ; Zammit, S. ; Schumacher, J. ; Quinn, E. M. ; Schulze, T. G. ; Iwata, N. ; Ikeda, M. ; Darvasi, A. ; Shifman, S. ; He, L. ; Duan, J. ; Sanders, A. R. ; Levinson, D. F. ; Adolfsson, R. ; Ösby, U. ; Terenius, L. ; Jönsson, E. G. ; Cichon, S. ; Nöthen, M. M. ; Gill, M. ; Corvin, A. P. ; Rujescu, D. ; Gejman, P. V. ; Kirov, G. ; Craddock, N. ; Williams, N. M. ; Owen, M. J. ; Gejman, P. V. ; Sanders, A. R. ; Duan, J. ; Levinson, D. F. ; Buccola, N. G. ; Mowry, B. J. ; Freedman, R. ; Amin, F. ; Black, D. W. ; Silverman, J. M. ; Byerley, W. J. ; Cloninger, C. R. / Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. In: Molecular Psychiatry. 2009 ; Vol. 14, No. 1. pp. 30-36.
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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.",
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.}",
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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

Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. / 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.; Shi, Y.; Feng, G.; Hoffmann, P.; Propping, P.; Vasilescu, C.; Maier, W.; Rietschel, M.; Zammit, S.; Schumacher, J.; Quinn, E. M.; Schulze, T. G.; Iwata, N.; Ikeda, M.; Darvasi, A.; Shifman, S.; He, L.; Duan, J.; Sanders, A. R.; Levinson, D. F.; Adolfsson, R.; Ösby, U.; Terenius, L.; Jönsson, E. G.; Cichon, S.; Nöthen, M. M.; Gill, M.; Corvin, A. P.; Rujescu, D.; Gejman, P. V.; Kirov, G.; Craddock, N.; Williams, N. M.; Owen, M. J.; Gejman, P. V.; Sanders, A. R.; Duan, J.; Levinson, D. F.; Buccola, N. G.; Mowry, B. J.; Freedman, R.; Amin, F.; Black, D. W.; Silverman, J. M.; Byerley, W. J.; Cloninger, C. R.

In: Molecular Psychiatry, Vol. 14, No. 1, 25.01.2009, p. 30-36.

Research output: Contribution to journal › Article

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.

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.

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U2 - 10.1038/mp.2008.108

DO - 10.1038/mp.2008.108

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EP - 36

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

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ER -

O'Donovan MC, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I et al. Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. Molecular Psychiatry. 2009 Jan 25;14(1):30-36. https://doi.org/10.1038/mp.2008.108

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