The study was led by the Bipolar Disorder Working Group at the Psychiatric Genomics Consortium, an international group made up of more than 800 researchers from 40 countries in which professionals from IDIBAPS-Hospital Clínic and Hospital Vall d’Hebron participate, all of them 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 characterised by the alternation of depressive episodes and episodes of mania or hypomania (euphoric or irritable moods). It can have a profound impact on daily life if not treated properly and poses a significant public health problem.
It has a substantial genetic basis, with an estimated heritability of between 60% and 80%. However, identifying the specific genes involved in this disorder has been a great challenge due to its complexity, as it combines genetic and environmental factors.
Genetic characterisation of bipolar disorder
The international group conducted a meta-analysis of several genome-wide association studies, combining their results to more accurately identify the genetic variants associated with a disease or a trait. In total, more than 158,000 patients with bipolar disorder and 2.8 million people without the disorder were included and the genes of the two groups were compared to decipher the existing differences. The most important feature is that people from all six inhabitable continents were included for the first time.
The study identified 337 variants of genome-wide significance (GWS) that are mutually independent and grouped into 298 specific regions of the genome (loci). This identification is four times larger than that of any previous study. These genetic variants are related to the causes of the disorder, as well as to brain plasticity and signal transmission.
By combining the results of advanced genetic mapping techniques, like fine-mapping and other strategies to link genetic variants with specific genes, the researchers identified 36 reliable genes related to the causes or development of bipolar disorder.
The researchers also found genetic differences, depending on the patients’ subtype of bipolar disorder. For instance, they found a greater genetic relationship with schizophrenia in the cohorts with a large proportion of patients with type 1 bipolar disorder. In the cohort with more cases of patients with type 2 bipolar disorder, they detected a greater genetic correlation with major depressive disorder and attention deficit hyperactivity disorder (ADHD).
‘With this study, we have taken a big step forward to better understand how this disorder functions and what causes it. Given a little more time, we also hope to develop new and better treatments for it’, says Dr Eduard Vieta, the head of Hospital Clínic’s Psychiatry Service and of the IDIBAPS research group Bipolar and depressive disorders.
Study reference:
Characterising the genetic landscape of bipolar disorder yields novel biological insights. Nature. DOI: https://www.nature.com/articles/s41586-024-08468-9
