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A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42

Abstract

In this study, we report a genome scan for psychiatric disease susceptibility loci in 13 Scottish families. We follow up one of the linkage peaks on chromosome 1q in a substantially larger sample of 22 families affected by schizophrenia (SCZ) or bipolar affective disorder (BPAD). To minimise the effect of genetic heterogeneity, we collected mainly large extended families (average family size >18). The families collected were Scottish, carried no chromosomal abnormalities and were unrelated to the large family previously reported as segregating a balanced (1 : 11) translocation with major psychiatric disease. In the genome scan, we found linkage peaks with logarithm of odds (LOD) scores >1.5 on chromosomes 1q (BPAD), 3p (SCZ), 8p (SCZ), 8q (BPAD), 9q (BPAD) and 19q (SCZ). In the follow-up sample, we obtained most evidence for linkage to 1q42 in bipolar families, with a maximum (parametric) LOD of 2.63 at D1S103. Multipoint variance components linkage gave a maximum LOD of 2.77 (overall maximum LOD 2.47 after correction for multiple tests), 12 cM from the previously identified SCZ susceptibility locus DISC1. Interestingly, there was negligible evidence for linkage to 1q42 in the SCZ families. These results, together with results from a number of other recent studies, stress the importance of the 1q42 region in susceptibility to both BPAD and SCZ.

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Acknowledgements

Financial support was provided by the Medical Research Council (UK), The Biotechnology and Biological Sciences Research Council (UK), The Chief Scientist Office of the Scottish Executive, the Royal Society and Akzo-Nobel (Organon). We are indebted to all the other participants in the European Science Foundation Program on Molecular Neurobiology of Mental Illnesses for being the initial stimulus to these studies.

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Correspondence to S Macgregor.

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Macgregor, S., Visscher, P., Knott, S. et al. A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42. Mol Psychiatry 9, 1083–1090 (2004). https://doi.org/10.1038/sj.mp.4001544

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