Researchers identify 36 genes linked to the onset and development of bipolar disorder

The study was led by the Bipolar Disorder Working Group at the Psychiatric Genomics Consortiuman international group made up of more than 800 researchers from 40 countries, with the participation of professionals from the IDIBAPS Hospital Clínic and the Hospital Vall d’Hebron, all researchers from CIBER de Salud Mental (CIBERSAM).

A disorder with a high genetic component

Bipolar disorder is a chronic mental disorder that affects between 40 and 50 million people worldwide and is characterized by the alternation of depressive episodes and episodes of mania or hypomania (euphoric or irritable mood). If not treated properly, it can have a profound impact on daily life and represents a significant public health problem.

It has one essential genetic basiswith an estimated heritability between 60% and 80%. However, due to its complexity as it combines genetic and environmental factors, identifying the specific genes involved in this disorder represents a major challenge.

Genetic characterization of bipolar disorder

The international group led a Meta-analysis of several genome-wide association studiesby combining their results to more accurately identify the genetic variants associated with a disease or trait. Overall, more than 158,000 patients with bipolar disorder and 2.8 million people without this disorder were included and the genes of the two groups were compared in order to decipher the existing differences. The most important feature is that, for the first time, people from all six inhabitable continents were included.

The study identified 337 Variants of genome-wide significance (GWS) these are independent of each other and grouped into 298 specific regions of the genome (loci). The The identification is four times greater than any previous study. These genetic variants are linked to the causes of the disorder as well as to brain plasticity and signaling.

By combining the results of advanced genetic mapping techniques, such as Fine mapping and other strategies to link genetic variants to specific genes, the researchers identified 36 reliable genes in connection with the Causes or development of bipolar disorder.

The researchers also found genetic differences depending on the patients’ bipolar disorder subtype. For example, they found a greater genetic association with schizophrenia in the cohorts with a large proportion of patients with bipolar type 1 disorder. In the cohort with more cases of patients with bipolar type 2 disorder, they found a greater genetic correlation with major depressive disorder and attention deficit hyperactivity disorder (ADHD).

“With this study, we have taken a big step forward in better understanding how this disorder works and what causes it.” With a little more time, we also hope to develop new and better treatments for it,” says Dr Edward VietaHead of the Psychiatric Service at the Hospital Clinic and the IDIBAPS Bipolar and Depressive Disorders Research Group.

Study reference:

Characterizing the genetic landscape of bipolar disorder provides new biological insights. Nature. DOI: https://www.nature.com/articles/s41586-024-08468-9