Genetic variants responsible for psychiatric disorders susceptibility

Genetic variants responsible for psychiatric disorders susceptibilityGenetic variants responsible for psychiatric disorders susceptibility

 

E. Docampo, M. Gratacòs, G. Escaramís, H. Hor, M. Morell, A. Puig, D. Trujillano

The group has developed activities in the study of substance abuse disorder, anxiety disorders (panic di- sorder and obsessive-compulsive disorder), eating disorders and affective disorders. In most cases, the methodology involved the selection of variants in genes known to be involved in the pathophysiology of these diseases. In particular, we have characterized the role of the BDNF Val66Met variant in melancholic depression and obsessive-compulsive disorder, and we have performed further studies on the FTO gene in bulimia and anorexia nervosa.

Furthermore, we are participating in a large GWAS for anorexia that is currently in the last phases of the analysis. We have studied samples of patients with different addictions to perform an association study targeting gene family of neurexins to assess the possible involvement of variants in these genes in addictive processes, where we have detected an association of NRXN3 variants with smoking behavior. In addition to these lines of research, the group has established inter- national partnerships to replicate the results of other investigations and contribute to studies of GWAS.

In an effort to find both rare and common variants involved in OCD, we are sequencing the exome of patients with severe and early onset of the disorder, including patients with family history of OCD, early age at onset, severe cases, and patients with good prognosis. The high depth of sequencing achieved allowed us to confidently mine the data for novel SNVs and short InDels discovery. After various filtering steps, we have selected a panel of genes that we have resequenced in a large cohort of cases and controls. All this resulted in the identification various genes and pathways that have a higher number of damaging SNVs in OCD patients than in on-OCD subjects. The approach used in OCD is being applied also to fibromyalgia cases that are very well characterized at the clinical level, with a very close followup of disease evolution.