1. ¹King's College London, Department of Medical and Molecular Genetics, London, UK
2. ²Department of Psychiatry, Stanford University, Stanford, CA, USA
3. ³Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
4. ⁴Washington University in St Louis, St Louis, MO, USA
5. ⁵Department of Psychiatry, The New York University Langone Medical Center, New York, NY, USA
6. ⁶Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY, USA
7. ⁷Department of Medical Genetics, University of Tsukuba, Tsukuba, Japan
8. ⁸Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
9. ⁹National Public Health Institute, Helsinki, Finland
10. ¹⁰Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
11. ¹¹Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
12. ¹²Department of Psychiatry, University of Indonesia, Jakarta, Indonesia
13. ¹³Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK
14. ¹⁴University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
15. ¹⁵Center for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia
16. ¹⁶Department of Child Psychiatry, Université Pierre et Marie Curie and Hôpital de la Pitiè-Salpêtrière, Paris, France
17. ¹⁷Queensland Centre for Mental Health Research and University of Queensland, Brisbane, QLD, Australia
18. ¹⁸Department of Genetics, Rutgers University, Piscataway, NJ, USA
19. ¹⁹Department of Psychiatry, Laval University & Centre de recherche Université Laval Robert-Giffard, Québec, QC, Canada
20. ²⁰Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
21. ²¹VA Medical Center, Asheville, NC, USA
22. ²²Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
23. ²³Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
24. ²⁴Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
25. ²⁵Department of Mental Health Sciences, University College London, London, UK
26. ²⁶Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute and Northwestern University, Evanston, IL, USA
27. ²⁷Department of Development & Genetics, Uppsala University, Uppsala, Sweden
28. ²⁸University of Kiel, Kiel, Germany
29. ²⁹University of California, San Francisco, CA, USA
30. ³⁰Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA
31. ³¹Center for Behavioral Genomics and Department of Psychiatry, University of California, San Diego, CA, USA
32. ³²Harvard Institute of Psychiatric Epidemiology & Genetics, Boston, MA, USA
33. ³³National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
34. ³⁴Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
35. ³⁵Washington VA Medical Center, Washington, DC, USA
36. ³⁶Department of Psychiatry, Georgetown University Medical Center, Virginia Commonwealth University, Richmond, VA, USA
37. ³⁷The Health Research Board, Dublin, Ireland
38. ³⁸Department of Psychiatry, Queens University, Belfast, Northern Ireland
39. ³⁹Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
40. ⁴⁰Department of Medical Genetics, University of Helsinki, Helsinki, Finland
41. ⁴¹The Broad Institute, MIT, Boston, MA, USA
42. ⁴²Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
43. ⁴³Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
44. ⁴⁴1st Department of Psychiatry, University of Athens Medical School, and University Mental Health Research Institute, Athens, Greece
45. ⁴⁵Western Australian Institute for Medical Research, University of Western Australia, Perth, WA, Australia
46. ⁴⁶School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia
47. ⁴⁷School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
48. ⁴⁸School of Biology and CIBCM, University of Costa Rica, San Jose, Costa Rica
49. ⁴⁹Carracci Medical Group and Universidad Autonoma de la Ciudad de Mexico, Mexico City, Mexico
50. ⁵⁰State Mental Hospital, Haar, Germany
51. ⁵¹Department of Psychiatry, University of Bonn, Bonn, Germany
52. ⁵²Departments of Psychiatry and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
53. ⁵³Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
54. ⁵⁴Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Centre National de la Recherche Scientifique, Hôpital de la Pitié Salpêtrière, Paris, France
55. ⁵⁵Department of Child Psychiatry, Université Pierre et Marie Curie and Hôpital de la Pitiè-Salpêtrière, Paris, France
56. ⁵⁶INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris, France
57. ⁵⁷Queensland Centre for Mental Health Research and University of Queensland, Brisbane, QLD, Australia
58. ⁵⁸Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
59. ⁵⁹Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
60. ⁶⁰Clinical Genetics Research Program, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
61. ⁶¹Center for Genomic Psychiatry, University of Southern California, Los Angeles, CA, USA
62. ⁶²Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Pretoria, Republic of South Africa
63. ⁶³Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
64. ⁶⁴Department of Psychological Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, London, UK
65. ⁶⁵Department of Psychiatry, General Hospital, Reykjavik, Iceland
66. ⁶⁶Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA
67. ⁶⁷Departments of Psychiatry and Genetics & Development, Columbia University Medical Center, New York, NY, USA
68. ⁶⁸King's College London, MRC SGDP Centre, Institute of Psychiatry, London, UK

Correspondence: Dr CM Lewis, Department of Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. E-mail: Cathryn.lewis@kcl.ac.uk

Received 9 October 2008; Accepted 11 November 2008; Published online 30 December 2008.

Abstract

A genome scan meta-a nalysis (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.