1. ¹Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK
2. ²Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
3. ³Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
4. ⁴School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia
5. ⁵Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, Mt Claremont, WA, Australia
6. ⁶Center for Psychiatric Genetics, Evanston Northwestern Healthcare Research Institute, Northwestern University, Evanston, IL, USA
7. ⁷Queensland Centre for Mental Health Research, University of Queensland, Brisbane, QLD, Australia
8. ⁸Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine, Paris, France
9. ⁹School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
10. ¹⁰Centre for Medical Research, Western Australian Institute for Medical Research, University of Western Australia, Perth, WA, Australia
11. ¹¹Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Centre National de la Recherche Scientifique, Hôpital de la Pitié Salpêtrière, Paris, France
12. ¹²State Mental Hospital, Haar, Germany
13. ¹³Department of Psychiatry, Stanford University, Stanford, CA, USA
14. ¹⁴INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris, France
15. ¹⁵Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
16. ¹⁶Department of Psychiatry, University of Bonn, Bonn, Germany
17. ¹⁷Department of Psychiatry, University of Athens Medical School, Athens, Greece
18. ¹⁸The Health Research Board, Dublin, Ireland
19. ¹⁹Department of Psychiatry, Queens University, Belfast, Ireland
20. ²⁰Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
21. ²¹Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, IW, USA
22. ²²Department of Psychiatry, Mt Sinai School of Medicine, New York, NY, USA

Correspondence: Dr DF Levinson, Department of Psychiatry, Stanford University, Suite A-3325, 701 Welch Road, Palo Alto, CA 94305, USA. E-mail: dflev@stanford.edu

Received 9 October 2008; Revised 20 November 2008; Accepted 25 November 2008; Published online 17 February 2009.

Abstract

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker–marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.