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PMID: 19349958 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Molecular psychiatry ·Vol. 14 ·No. 8 ·2009-08-00 ·Pages 774-85

Ng MY, Levinson DF, Faraone SV, Suarez BK, DeLisi LE, Arinami T, Riley B, Paunio T, Pulver AE, Irmansyah, 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 HM, Gejman PV, Lindholm E, Moises HW, Byerley W, Wijsman EM, Forabosco P, Tsuang MT, Hwu HG, 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 MA, Mérette 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

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.

MeSH Terms
Chromosomes, Human/genetics Female Genetic Linkage Genetic Predisposition to Disease Genome, Human/genetics Genome-Wide Association Study/methods Humans Lod Score Male Pedigree Schizophrenia/genetics
Authors & Affiliations
82 authors, click to expand affiliations / ORCID
Ng M Y M
King's College London, Department of Medical and Molecular Genetics, London, UK.
Levinson D F
Faraone S V
Suarez B K
DeLisi L E
Arinami T
Riley B
Paunio T
Pulver A E
Irmansyah
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
Abecasis G R
Lerer B
Fallin M D
Gurling H M D
Gejman P V
Lindholm E
Moises H W
Byerley W
Wijsman E M
Forabosco P
Tsuang M T
Hwu H-G
Okazaki Y
Kendler K S
Wormley B
Fanous A
Walsh D
O'Neill F A
Peltonen L
Nestadt G
Lasseter V K
Liang K Y
Papadimitriou G M
Dikeos D G
Schwab S G
Owen M J
O'Donovan M C
Norton N
Hare E
Raventos H
Nicolini H
Albus M
Maier W
Nimgaonkar V L
Terenius L
Mallet J
Jay M
Godard S
Nertney D
Alexander M
Crowe R R
Silverman J M
Bassett A S
Roy M-A
Mérette C
Pato C N
Pato M T
Roos J Louw
Kohn Y
Amann-Zalcenstein D
Kalsi G
McQuillin A
Curtis D
Brynjolfson J
Sigmundsson T
Petursson H
Sanders A R
Duan J
Jazin E
Myles-Worsley M
Karayiorgou M
Lewis C M
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Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
DOI
10.1038/mp.2008.135
Published
2009-08-00
Epub
2008-00-30
Pages
774-85
Language
English
Region
England
NLM ID
9607835
PMCID
PMC2715392
Subset
IM
Grants
Wellcome Trust · 055379 · United Kingdom
NIMH NIH HHS · 5 U01MH46318 · United States
NIMH NIH HHS · U01 MH046276 · United States
NIMH NIH HHS · R01 MH041953-14 · United States
NIMH NIH HHS · R01 MH060875 · United States
NIMH NIH HHS · R01 MH062276 · United States
NIMH NIH HHS · MH 56242 · United States
NIMH NIH HHS · R01 MH080299 · United States
NIMH NIH HHS · U01 MH046289 · United States
Medical Research Council · G880473N · United Kingdom
Wellcome Trust · 089061 · United Kingdom
NIMH NIH HHS · R01-MH44245 · United States
NIMH NIH HHS · 7R01MH062276 · United States
NHLBI NIH HHS · N01HV48141 · United States
NIMH NIH HHS · MH062440 · United States
NIMH NIH HHS · 5R01MH068881 · United States
NIMH NIH HHS · 1R01 MH59624-01 · United States
NIMH NIH HHS · MH60881 · United States
NIMH NIH HHS · MH80299 · United States
Medical Research Council · G9309834 · United Kingdom
NIMH NIH HHS · R01 MH041953-10 · United States
NIMH NIH HHS · R10 MH056242 · United States
NIMH NIH HHS · R01 MH041953-09A2 · United States
NIMH NIH HHS · MH61399 · United States
NIMH NIH HHS · R01 MH041953-17 · United States
NIMH NIH HHS · MH58586 · United States
NIMH NIH HHS · 5R01MH068922 · United States
NIMH NIH HHS · R01 MH060881 · United States
NIMH NIH HHS · R01 MH062440 · United States
NIMH NIH HHS · R01 MH061399 · United States
NIMH NIH HHS · 5R01MH068921 · United States
NIMH NIH HHS · R01 MH068881 · United States
NIMH NIH HHS · R01 MH041953-16 · United States
NIMH NIH HHS · R01 MH041953-11 · United States
NIMH NIH HHS · R01 MH041953-08S1 · United States
NIMH NIH HHS · R01 MH068922 · United States
NIMH NIH HHS · R01 MH041953 · United States
NIMH NIH HHS · R01 MH041953-13 · United States
NIMH NIH HHS · MH63356 · United States
NIMH NIH HHS · R01 MH041953-15 · United States
NIMH NIH HHS · MH-41953 · United States
NIMH NIH HHS · R01 MH068921 · United States
NIMH NIH HHS · MH60875 · United States
NIMH NIH HHS · R01 MH063356 · United States
NIMH NIH HHS · U01 MH046318 · United States
Medical Research Council · G0801418 · United Kingdom
Medical Research Council · G0400960 · United Kingdom
NIMH NIH HHS · R01 MH056242 · United States
NIMH NIH HHS · R01 MH041953-12 · United States
External Links
PubMed source DOI: 10.1038/mp.2008.135 PMC Full Text View journal details
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