MOLECULAR GENETICS OF BIPOLAR AFFECTIVE DISORDER

The research project aims to contribute to the understanding of the basic genetic causes of bipolar disorder and genetically related unipolar disorder. These disorders are strongly associated with alcoholism and other drugs of abuse. Therefore the understanding of the genetic cases of bipolar and related unipolar affective disorders will also contribute to the understanding of one of the many causes of alcoholism. The finding of genes increasing susceptibility to bipolar disorder is not an academic exercise because the science can point to new approaches for designing drugs for depression and mania. Preventive measures are also possible once it is possible to understand the underlying causes.

A case control sample of 2,000 bipolar affective disorder cases and 2,000 controls will be used for further research into the genetic variation causing susceptibility to bipolar and genetically related unipolar affective disorders. The aim is to use the genetic information to understand the molecular pathology in the brain and to design better treatment and preventive strategies. We have already identified several susceptibility genes in the UCL sample and have partially sequenced the DNA of the ANKYRIN3, GRM7, SLC1A2, TRPM2, SLYNAR and IGF1 genes. We now wish to carry out further exploration of potential aetiological base pair variants found in these genes by genotyping them in the whole enlarged case control sample. In the case of the SYNE1, ANKYRIN3, GRM7 and SLC1A2 genes we wish to extend this sequencing using high through put methods in a greater number of cases as well as to continue sequencing several further genes which are strongly associated with bipolar disorder in the UCL sample. In addition we now wish to make further use of the family lineality and sex of parent transmission data we have in order to find subgroups of cases showing major gene transmission and susceptibility genes which have methylation patterns that correlate with parental sex of transmission. We also wish to explore the genetic role of afective disorder genes in a case control sample of the alcohol dependence syndrome. Lastly we wish to continue to contribute to international collaborations that are generating large enough sample sizes to fully explore the relationship between genetic effects and clinical variables such as prognosis and response to treatment.