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Vall d'Hebron participates in a study that identifies 33 new genetic variants associated with bipolar disorder

Josep Antoni Ramos Quiroga
Monday, 17 May, 2021

These findings open the way for research into new therapeutic targets, as well as for the study of the possibility of reusing drugs that are already used in other illnesses for the treatment of bipolar disorder.

The largest study on the heritability of bipolar disorder carried out to date has allowed the identification of 33 new genetic variants related to this mental pathology, which also represent a turning point to advance in the discovery of therapeutic targets and drugs for its treatment. This international collaborative research, whose results are published today in the journal Nature Genetics, has been co-led by Dr. Josep Antoni Ramos-Quiroga, from the Psychiatry Service of the Vall d'Hebron University Hospital and the Psychiatry, Mental Health and Addictions group of the Vall d'Hebron Research Institute (VHIR). The study is also co-led by Dr. Eduard Vieta from Hospital Clínic-IDIBAPS. Both researchers are part of the CIBER de Salud Mental (CIBERSAM) and the study is part of the Working Group on Bipolar Disorder of the Psychiatric Genomics Consortium.

Bipolar disorder is a complex mental illness characterized by the pathological alternation of depressive-type episodes with mood episodes of the opposite nature known as mania or hypomania. It is estimated that this disease affects between 40-50 million people worldwide. This chronic mental illness has a very relevant impact on the day-to-day life of those who suffer from it and is associated with ongoing complications that can cause deterioration in multiple areas of life if not treated properly, which makes it a very relevant public health problem.

Bipolar disorder, a highly heritable pathology

Numerous studies have shown that the onset of this disease is due to the complex interaction of both biological and environmental factors, having shown that heritability is very significant, estimated at around 60-85%. However, identifying the genetic variants involved in the disorder is an arduous task, given that the scientific evidence collected so far indicates that there are multiple associated genes.

In recent years, the development of new research techniques is allowing the massive analysis of genetic information, leading to advances that, little by little, will help the scientific community to more accurately determine the origin and biological mechanisms involved in both the debut and the evolution of the clinical course of said disease.

The largest study on the genetics of bipolar disorder

This has been the objective of this international collaborative study carried out by the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, which delves into a better understanding of the genetics of this disorder. In it, the researchers studied more than 7.5 million common variations in the DNA sequence of nearly 415,000 people, of whom more than 40,000 had bipolar disorder.

"This is the most complete genetic study in history on the heritability of bipolar disorder, and its results open a way to better understand how this disorder is transmitted and develop new treatments", says Dr. Eduard Vieta, scientific director of CIBERSAM, Head of the Department of Psychiatry at the Hospital Clínic-IDIBAPS and professor at the University of Barcelona.

As a result of this research, the most ambitious and extensive carried out in this field, 64 genetic variants were detected, 33 of which were totally new, associated with bipolar disorder. Specifically, variants were found in genes involved in specific biological pathways related to neuronal communication and calcium signaling, both of which are highly relevant for an optimal functioning of the central nervous system.

Genes common to other psychiatric disorders

The study also detected genetic loci (places where genes are located) previously associated with other psychiatric pathologies, especially related to schizophrenia and major depression, and to a lesser degree with other disorders such as anorexia, attention deficit disorder and hyperactivity (ADHD) and autism spectrum disorder, as well as smoking, problematic alcohol use, and poor sleep quality.

Likewise, the research detected an association in bipolar disorder with genetic targets targeted by drugs already used for the treatment of other diseases, such as antipsychotics, mood stabilizers and antiepileptics, anesthetics, or channel blockers. calcium used to treat hypertension.

"All these findings open up new avenues of research regarding the generation of new therapeutic targets, as well as for the study of the possibility of reusing some drugs that are used with other types of ailment to treat bipolar disorder", explains Dr. Josep Antoni Ramos-Quiroga, head of the Psychiatry Service of the Vall d'Hebron University Hospital and the Psychiatry, Mental Health and Addictions group of the Vall d'Hebron Research Institute (VHIR) and principal investigator of the CIBERSAM.

Other Spanish researchers attached to IBIMA, the Autonomous University of Barcelona, ​​the University of Barcelona, ​​the University of Granada and ISGlobal have also participated in this research.

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