DNA helix rollercoaster representing the genetic search for bipolar disorder.

Unlocking Bipolar Disorder: Can Genetics Lead the Way?

"A new study dives deep into the exome to find potential genetic risk factors for bipolar disorder, offering hope for early detection and personalized treatments."


Bipolar I disorder (BD) is a complex mental health condition marked by dramatic shifts in mood, swinging between highs of mania and lows of depression. These mood swings can significantly disrupt daily life, impacting relationships, work, and overall well-being. The condition often emerges in early adulthood and can lead to severe consequences if left unmanaged; up to 15% of those affected may consider suicide.

While the exact causes of bipolar disorder are still being investigated, research strongly suggests a genetic component. Family, twin, and adoption studies have consistently shown that genes play a significant role in determining who develops the condition. This has spurred scientists to search for specific genes that contribute to the risk of bipolar disorder, hoping to unlock new avenues for treatment and prevention.

Now, a new study published in Translational Psychiatry explores the role of rare genetic variants in bipolar disorder. By sequencing the entire exome (the protein-coding part of the genome) of individuals with bipolar disorder and comparing them to healthy controls, researchers are uncovering potential genetic risk factors that could revolutionize our understanding and treatment of this challenging condition.

Searching for Risk Genes in the Exome

DNA helix rollercoaster representing the genetic search for bipolar disorder.

The study, conducted by researchers in France, involved sequencing the exomes of 92 individuals diagnosed with bipolar I disorder and comparing them to 1051 control individuals of French ancestry. To increase the likelihood of finding relevant genetic variants, the researchers focused on individuals with an "extreme phenotype" – those who experienced an earlier onset of bipolar disorder and had a strong family history of mood disorders.

The researchers used a technique called "collapsing strategy" to analyze the data. This involved grouping together rare genetic variants within each gene and then comparing the overall burden of these rare variants between the bipolar disorder group and the control group. Only variants predicted to have a damaging effect on protein function were included in the analysis.

  • Whole-Exome Sequencing (WES): Analyzing the entire protein-coding region of the genome to identify rare variants.
  • Collapsing Strategy: Grouping rare variants within genes to increase statistical power.
  • Extreme Phenotype: Focusing on individuals with early onset and strong family history to enrich for genetic factors.
The study identified 13 genes that showed a suggestive association with bipolar disorder, meaning they had a higher burden of rare, damaging variants in the bipolar disorder group compared to the control group. While these genes didn't reach the stringent threshold required to declare genome-wide significance, they offer promising leads for future research.

What Does This Mean for Bipolar Disorder?

The identified genes are involved in various brain processes, some of which have been previously linked to bipolar disorder. Interestingly, several of these genes belong to pathways that are affected by lithium, a common mood stabilizer used to treat bipolar disorder. This suggests that these genes may play a role in how lithium exerts its therapeutic effects.

While the study didn't pinpoint any single gene with conclusive evidence, it highlights the potential of using whole-exome sequencing to uncover genetic risk factors for bipolar disorder. The findings suggest that a combination of rare genetic variants may contribute to the development of the condition, rather than a single, dominant gene.

The researchers emphasize that larger studies are needed to confirm these findings and identify additional risk genes. However, this study represents an important step forward in understanding the genetic basis of bipolar disorder, paving the way for more targeted and personalized treatments in the future. Imagine a future where genetic testing can help identify individuals at risk for bipolar disorder, allowing for early intervention and potentially preventing the onset of the condition. This research brings us closer to that reality.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1038/s41398-018-0291-7, Alternate LINK

Title: Identification Of Potential Genetic Risk Factors For Bipolar Disorder By Whole-Exome Sequencing

Subject: Biological Psychiatry

Journal: Translational Psychiatry

Publisher: Springer Science and Business Media LLC

Authors: Thomas Husson, Jean-Baptiste Duboc, Olivier Quenez, Camille Charbonnier, Maud Rotharmel, Macarena Cuenca, Xavier Jegouzo, Anne-Claire Richard, Thierry Frebourg, Jean-François Deleuze, Anne Boland, Emmanuelle Genin, Stéphanie Debette, Christophe Tzourio, Dominique Campion, Gaël Nicolas, Olivier Guillin

Published: 2018-12-01

Everything You Need To Know

1

What exactly is Bipolar I disorder, and what are the implications of the condition?

Bipolar I disorder (BD) is a complex mental health condition characterized by dramatic shifts in mood, including periods of mania and depression. The implications of this condition include significant disruptions to daily life, relationships, and overall well-being. Untreated, Bipolar I disorder can lead to severe consequences including suicidal ideation.

2

What is Whole-Exome Sequencing (WES), and how is it used in studying Bipolar I disorder?

Whole-Exome Sequencing (WES) is a technique used to analyze the entire protein-coding region of the genome, called the exome. In the context of understanding Bipolar I disorder, WES is used to identify rare genetic variants that may contribute to the risk of developing the condition. By analyzing the exome, researchers can pinpoint specific genes that could be linked to the disorder, paving the way for targeted treatments.

3

What is the Collapsing Strategy, and why is it used in this research?

The Collapsing Strategy is a method used in genetic studies to analyze the data. It involves grouping together rare genetic variants within each gene and then comparing the overall burden of these variants between different groups of individuals. Researchers used this method to compare individuals with Bipolar I disorder to control individuals. This strategy increases the statistical power to detect associations between genetic variants and the disorder.

4

What is meant by an Extreme Phenotype in the context of this study?

An Extreme Phenotype refers to the characteristics of individuals with an earlier onset of Bipolar I disorder and a strong family history of mood disorders. Researchers focused on this group to enrich for genetic factors, increasing the likelihood of finding relevant genetic variants associated with the condition. This approach helps to narrow the search and identify genes with a greater impact on the development of Bipolar I disorder.

5

What were the key findings regarding the genes associated with Bipolar I disorder?

The study identified 13 genes that showed a suggestive association with Bipolar I disorder. The genes are involved in various brain processes and some have previously been linked to the disorder. Notably, several of these genes belong to pathways that are affected by lithium, a common mood stabilizer. This suggests that the identified genes may play a role in how Lithium exerts its therapeutic effects.

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