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 Psychiatry

Research output: Contribution to journal › Article

52 Citations (Scopus)

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
Publication status	Published - 25-01-2009

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All Science Journal Classification (ASJC) codes

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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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

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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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.",

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.}",

year = "2009",

month = jan

day = "25",

doi = "10.1038/mp.2008.108",

language = "English",

volume = "14",

pages = "30--36",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

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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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10.1038/mp.2008.108