Susceptibility-Genes in Unipolar Depression

Unipolar depression is a very common disorder and is a major public health problem in the UK, as well as in Austria and throughout the world. There is good evidence from studies looking at families and twins that there is a substantial genetic contribution to depression, particularly recurrent disorder. Almost certainly the genetic component of depression results from many genes of small effect and there is also a complicated interplay with environmental factors such as distressing events. The aim of this project is to find susceptibility genes involved in unipolar depression by performing a two stage whole genome scan, with the first stage consisting of genotyping using microarrays and DNA pools and the second consisting of individual genotyping of the markers that show the most significant differences between groups. All depressed probands were given a face to face semi-structured diagnostic interview, the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) by trained interviewers to establish diagnoses according to DSM-IV and ICD-10 operational definitions. The first stage will use the new Affymetrix 500k GeneChip on DNA pools on a) a large clinical case-control collection, more precisely subjects from the Depression Case control (DeCC) study (1536 cases; approximately 1400 controls with collection continuing to a total of 1500) and b) 1165 unrelated subjects from the population based GENESiS study, whose scores fall within the top 10% and bottom 10% on a composite measure of depressive and anxiety symptoms. Markers that are positive in both sets of DNA pooling experiments will be followed up by individual genotyping in stage two. This will be carried out using the two sets of subjects from the first stage a) and b), plus an independent case control replication sample. Finding genes involved in depression has great potential benefits for clinical practice, first in better understanding the biology of depression and thereafter in discovering better, safer medications.