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  • Original Research Article
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Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

Molecular Psychiatry volume 10, pages 486–499 (2005)Cite this article

Abstract

The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N=480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels × 2 models of transmission × 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score >4.0: three for BP (15q11.1, 16p12.3, 18q12–q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12–q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores >1.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects.

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Acknowledgements

We dedicate this research to the memory of the late Professor Theodore Reich. This research was supported in part by a group grant (#MGC-14501) from the Canadian Institutes of Health Research (CIHR) and another individual CIHR grant (# MT-12854), and also by a Canada Research Chair (# 950-200810) in psychiatric genetics of which Maziade is the Chairholder. Roy and Mérette are each supported by a scholarship from the Fonds de la recherche en santé du Québec (FRSQ). We thank the families for their participation. We are also grateful to our professional research assistants: Louise Bélanger, Suzanne Belzile, Céline Blackburn, Pierrette Boutin, Liliane Charron, Jeannine Landry, Claudie Poirier, Linda René, Véronique Tremblay, Johanne Trépanier and Marjolaine Turgeon.

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  1. Department of Psychiatry, Laval University, Quebec, Canada

    M Maziade, M-A Roy, Y C Chagnon, D Cliche, J-P Fournier, N Montgrain, C Dion, J-C Lavallée, Y Garneau, N Gingras, L Nicole, A Pirès, A-M Ponton, A Potvin, H Wallot & C Mérette

  2. Centre de recherche Université Laval Robert-Giffard, Beauport, Quebec, Canada

    M Maziade, M-A Roy, Y C Chagnon, D Cliche, J-P Fournier, N Montgrain, C Dion, J-C Lavallée, Y Garneau, N Gingras, L Nicole, A Pirès, A-M Ponton, A Potvin, H Wallot & C Mérette

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Maziade, M., Roy, MA., Chagnon, Y. et al. Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families. Mol Psychiatry 10, 486–499 (2005). https://doi.org/10.1038/sj.mp.4001594

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  • DOI: https://doi.org/10.1038/sj.mp.4001594

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