Genome scan of pedigrees multiply affected with bipolar... : Psychiatric Genetics (original) (raw)

Original article

Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q

Curtis, Davida; Kalsi, Gursharanb; Brynjolfsson, Jonc; McInnis, Melvinc; O'Neill, Janeb; Smyth, Ciaranb; Moloney, Eamonnb; Murphy, Patriceb; McQuillin, Andrewb; Petursson, Hannesc; Gurling, Hughb

aJoint Academic Department of Psychological Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, London, UK,

bMolecular Psychiatry Laboratory, Windeyer Institute for Medical Science, Department of Psychiatry and Behavioral Sciences, Royal Free and University College Medical School, University College London, UK and

cDepartment of Psychiatry, General Hospital, Reykjavik, Iceland.

Sponsorship: The research was funded by Medical Research Council grant G9623693N, the Priory Hospital, London (research lectureship to Dr J Lawrence), the European Science Foundation, Schizophrenia A National Emergency (SANE), the Joseph Levy Charitable Foundation, the Wellcome Trust (Senior Fellowship to H.G., grant number 055379), the Neuroscience Research Charitable Trust, the Iceland Department of Health, the General Hospital Reykjavik, the University of Iceland and the Icelandic Science Council.

Correspondence to David Curtis, Department of Adult Psychiatry, 3rd Floor, Outpatient Building, Royal London Hospital, London E1 1BB, UK. Tel: + 44 20 7377 7729; fax: +44 20 7377 7316; e-mail: [email protected]

Received 4 April 2002 Accepted 17 July 2002

Abstract

Objective

To localize genes conferring susceptibility to bipolar affective disorder.

Methods

Seven families were selected on the basis of containing multiple cases of bipolar affective disorder present in three or more generations, an absence of schizophrenia and unilineal transmission. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10 cM intervals across the whole genome. All markers were subjected to initial two-point and three-point analyses using LOD score and model-free analysis. All regions producing a result significant at P<0.01 were then subjected to four-point LOD score analysis under the assumption of heterogeneity.

Results

A four-point LOD score of 2.8 was obtained using a dominant model and including unipolar cases as affected in the region of D12S342. Four-point LOD scores of 2 were obtained around D1S243, D1S251 and D3S1265. The positive results around D1S243 were accounted for by a LOD score of 3.1 occurring in a single pedigree.

Conclusions

Since there has been previous strong support for linkage to the region of 12q23-q24 around D12S342, it now seems very probable that it does indeed contain a gene influencing susceptibility to bipolar affective disorder. Some evidence for linkage in the region of 1q near to D1S251 has been reported in one previous study. It therefore seems that this region of 1q and the region of 1p close to D1S243 may also harbour susceptibility genes.