Meta-analysis of 32 genome-wide linkage studies of schizophrenia

M. Y. M. Ng; D. F. Levinson; S. V. Faraone; B. K. Suarez; L. E. DeLisi; T. Arinami; B. Riley; T. Paunio; A. E. Pulver; P. A. Holmans; M. Escamilla; D. B. Wildenauer; N. M. Williams; C. Laurent; B. J. Mowry; L. M. Brzustowicz; M. Maziade; P. Sklar; D. L. Garver; G. R. Abecasis; B. Lerer; M. D. Fallin; H. M. D. Gurling; P. V. Gejman; E. Lindholm; H. W. Moises; W. Byerley; E. M. Wijsman; P. Forabosco; M. T. Tsuang; H-G Hwu; Y. Okazaki; K. S. Kendler; B. Wormley; A. Fanous; D. Walsh; F. A. O'Neill; L. Peltonen; G. Nestadt; V. K. Lasseter; K. Y. Liang; G. M. Papadimitriou; D. G. Dikeos; S. G. Schwab; M. J. Owen; M. C. O'Donovan; N. Norton; E. Hare; H. Raventos; H. Nicolini; M. Albus; W. Maier; V. L. Nimgaonkar; L. Terenius; J. Mallet; M. Jay; S. Godard; D. Nertney; M. Alexander; R. R. Crowe; J. M. Silverman; A. S. Bassett; M-A Roy; C. Merette; C. N. Pato; M. T. Pato; J. Louw Roos; Y. Kohn; D. Amann-Zalcenstein; G. Kalsi; A. McQuillin; D. Curtis; J. Brynjolfson; T. Sigmundsson; H. Petursson; A. R. Sanders; J. Duan; E. Jazin; M. Myles-Worsley; M. Karayiorgou; C. M. Lewis

doi:10.1038/mp.2008.135

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

M. Y. M. Ng, D. F. Levinson, S. V. Faraone, B. K. Suarez, L. E. DeLisi, T. Arinami, B. Riley, T. Paunio, A. E. Pulver, P. A. Holmans, M. Escamilla, D. B. Wildenauer, N. M. Williams, C. Laurent, B. J. Mowry, L. M. Brzustowicz, M. Maziade, P. Sklar, D. L. Garver, G. R. AbecasisB. Lerer, M. D. Fallin, H. M. D. Gurling, P. V. Gejman, E. Lindholm, H. W. Moises, W. Byerley, E. M. Wijsman, P. Forabosco, M. T. Tsuang, H-G Hwu, Y. Okazaki, K. S. Kendler, B. Wormley, A. Fanous, D. Walsh, F. A. O'Neill, L. Peltonen, G. Nestadt, V. K. Lasseter, K. Y. Liang, G. M. Papadimitriou, D. G. Dikeos, S. G. Schwab, M. J. Owen, M. C. O'Donovan, N. Norton, E. Hare, H. Raventos, H. Nicolini, M. Albus, W. Maier, V. L. Nimgaonkar, L. Terenius, J. Mallet, M. Jay, S. Godard, D. Nertney, M. Alexander, R. R. Crowe, J. M. Silverman, A. S. Bassett, M-A Roy, C. Merette, C. N. Pato, M. T. Pato, J. Louw Roos, Y. Kohn, D. Amann-Zalcenstein, G. Kalsi, A. McQuillin, D. Curtis, J. Brynjolfson, T. Sigmundsson, H. Petursson, A. R. Sanders, J. Duan, E. Jazin, M. Myles-Worsley, M. Karayiorgou, C. M. Lewis

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Abstract

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008

Original language	English
Pages (from-to)	774 - 785
Number of pages	12
Journal	Molecular Psychiatry
Volume	14
Issue number	8
DOIs	https://doi.org/10.1038/mp.2008.135
Publication status	Published - Aug 2009

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Ng, M. Y. M., Levinson, D. F., Faraone, S. V., Suarez, B. K., DeLisi, L. E., Arinami, T., Riley, B., Paunio, T., Pulver, A. E., Holmans, P. A., Escamilla, M., Wildenauer, D. B., Williams, N. M., Laurent, C., Mowry, B. J., Brzustowicz, L. M., Maziade, M., Sklar, P., Garver, D. L., ... Lewis, C. M. (2009). Meta-analysis of 32 genome-wide linkage studies of schizophrenia. Molecular Psychiatry, 14(8), 774 - 785. https://doi.org/10.1038/mp.2008.135

@article{6aa2f4fe160c4d039c68886e00f29ab0,

title = "Meta-analysis of 32 genome-wide linkage studies of schizophrenia",

abstract = "A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008",

author = "Ng, {M. Y. M.} and Levinson, {D. F.} and Faraone, {S. V.} and Suarez, {B. K.} and DeLisi, {L. E.} and T. Arinami and B. Riley and T. Paunio and Pulver, {A. E.} and Holmans, {P. A.} and M. Escamilla and Wildenauer, {D. B.} and Williams, {N. M.} and C. Laurent and Mowry, {B. J.} and Brzustowicz, {L. M.} and M. Maziade and P. Sklar and Garver, {D. L.} and Abecasis, {G. R.} and B. Lerer and Fallin, {M. D.} and Gurling, {H. M. D.} and Gejman, {P. V.} and E. Lindholm and Moises, {H. W.} and W. Byerley and Wijsman, {E. M.} and P. Forabosco and Tsuang, {M. T.} and H-G Hwu and Y. Okazaki and Kendler, {K. S.} and B. Wormley and A. Fanous and D. Walsh and O'Neill, {F. A.} and L. Peltonen and G. Nestadt and Lasseter, {V. K.} and Liang, {K. Y.} and Papadimitriou, {G. M.} and Dikeos, {D. G.} and Schwab, {S. G.} and Owen, {M. J.} and O'Donovan, {M. C.} and N. Norton and E. Hare and H. Raventos and H. Nicolini and M. Albus and W. Maier and Nimgaonkar, {V. L.} and L. Terenius and J. Mallet and M. Jay and S. Godard and D. Nertney and M. Alexander and Crowe, {R. R.} and Silverman, {J. M.} and Bassett, {A. S.} and M-A Roy and C. Merette and Pato, {C. N.} and Pato, {M. T.} and Roos, {J. Louw} and Y. Kohn and D. Amann-Zalcenstein and G. Kalsi and A. McQuillin and D. Curtis and J. Brynjolfson and T. Sigmundsson and H. Petursson and Sanders, {A. R.} and J. Duan and E. Jazin and M. Myles-Worsley and M. Karayiorgou and Lewis, {C. M.}",

year = "2009",

month = aug,

doi = "10.1038/mp.2008.135",

language = "English",

volume = "14",

pages = "774 -- 785",

journal = "Molecular Psychiatry",

publisher = "Springer Nature [academic journals on nature.com]",

number = "8",

}

Ng, MYM, Levinson, DF, Faraone, SV, Suarez, BK, DeLisi, LE, Arinami, T, Riley, B, Paunio, T, Pulver, AE, Holmans, PA, Escamilla, M, Wildenauer, DB, Williams, NM, Laurent, C, Mowry, BJ, Brzustowicz, LM, Maziade, M, Sklar, P, Garver, DL, Abecasis, GR, Lerer, B, Fallin, MD, Gurling, HMD, Gejman, PV, Lindholm, E, Moises, HW, Byerley, W, Wijsman, EM, Forabosco, P, Tsuang, MT, Hwu, H-G, Okazaki, Y, Kendler, KS, Wormley, B, Fanous, A, Walsh, D, O'Neill, FA, Peltonen, L, Nestadt, G, Lasseter, VK, Liang, KY, Papadimitriou, GM, Dikeos, DG, Schwab, SG, Owen, MJ, O'Donovan, MC, Norton, N, Hare, E, Raventos, H, Nicolini, H, Albus, M, Maier, W, Nimgaonkar, VL, Terenius, L, Mallet, J, Jay, M, Godard, S, Nertney, D, Alexander, M, Crowe, RR, Silverman, JM, Bassett, AS, Roy, M-A, Merette, C, Pato, CN, Pato, MT, Roos, JL, Kohn, Y, Amann-Zalcenstein, D, Kalsi, G, McQuillin, A, Curtis, D, Brynjolfson, J, Sigmundsson, T, Petursson, H, Sanders, AR, Duan, J, Jazin, E, Myles-Worsley, M, Karayiorgou, M & Lewis, CM 2009, 'Meta-analysis of 32 genome-wide linkage studies of schizophrenia', Molecular Psychiatry, vol. 14, no. 8, pp. 774 - 785. https://doi.org/10.1038/mp.2008.135

TY - JOUR

T1 - Meta-analysis of 32 genome-wide linkage studies of schizophrenia

AU - Ng, M. Y. M.

AU - Levinson, D. F.

AU - Faraone, S. V.

AU - Suarez, B. K.

AU - DeLisi, L. E.

AU - Arinami, T.

AU - Riley, B.

AU - Paunio, T.

AU - Pulver, A. E.

AU - Holmans, P. A.

AU - Escamilla, M.

AU - Wildenauer, D. B.

AU - Williams, N. M.

AU - Laurent, C.

AU - Mowry, B. J.

AU - Brzustowicz, L. M.

AU - Maziade, M.

AU - Sklar, P.

AU - Garver, D. L.

AU - Abecasis, G. R.

AU - Lerer, B.

AU - Fallin, M. D.

AU - Gurling, H. M. D.

AU - Gejman, P. V.

AU - Lindholm, E.

AU - Moises, H. W.

AU - Byerley, W.

AU - Wijsman, E. M.

AU - Forabosco, P.

AU - Tsuang, M. T.

AU - Hwu, H-G

AU - Okazaki, Y.

AU - Kendler, K. S.

AU - Wormley, B.

AU - Fanous, A.

AU - Walsh, D.

AU - O'Neill, F. A.

AU - Peltonen, L.

AU - Nestadt, G.

AU - Lasseter, V. K.

AU - Liang, K. Y.

AU - Papadimitriou, G. M.

AU - Dikeos, D. G.

AU - Schwab, S. G.

AU - Owen, M. J.

AU - O'Donovan, M. C.

AU - Norton, N.

AU - Hare, E.

AU - Raventos, H.

AU - Nicolini, H.

AU - Albus, M.

AU - Maier, W.

AU - Nimgaonkar, V. L.

AU - Terenius, L.

AU - Mallet, J.

AU - Jay, M.

AU - Godard, S.

AU - Nertney, D.

AU - Alexander, M.

AU - Crowe, R. R.

AU - Silverman, J. M.

AU - Bassett, A. S.

AU - Roy, M-A

AU - Merette, C.

AU - Pato, C. N.

AU - Pato, M. T.

AU - Roos, J. Louw

AU - Kohn, Y.

AU - Amann-Zalcenstein, D.

AU - Kalsi, G.

AU - McQuillin, A.

AU - Curtis, D.

AU - Brynjolfson, J.

AU - Sigmundsson, T.

AU - Petursson, H.

AU - Sanders, A. R.

AU - Duan, J.

AU - Jazin, E.

AU - Myles-Worsley, M.

AU - Karayiorgou, M.

AU - Lewis, C. M.

PY - 2009/8

Y1 - 2009/8

N2 - A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008

AB - A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008

U2 - 10.1038/mp.2008.135

DO - 10.1038/mp.2008.135

M3 - Article

VL - 14

SP - 774

EP - 785

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 8

ER -

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

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