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Study identifies genetic signatures associated with bipolar disorder

DNA Molecule Structure

A study of over 415,000 research participants – including over 40,000 people with bipolar disorder (BD) – has identified 64 genomic regions that make people more susceptible to the condition.

The study, conducted by the Psychiatric Genomics Consortium, involved over 200 institutions from North America, Europe and Australia, including researchers from UNSW Sydney and Neuroscience Research Australia (NeuRA).

BD is a common mood disorder that affects around 350,000 Australians and an estimated 40 to 50 million people worldwide. This, combined with the typical onset in young adulthood – an often chronic life-long course and increased risk of suicide – makes BD a major public health concern and cause of global disability.

Until now, only a fraction of the genetic causes of BD has been identified, meaning the specific biological mechanisms that contribute to the development of the disorder continues to be of intense research interest.

Published this week in Nature Genetics, the study revealed the DNA locations of 64 genetic variations that increased the risk of BD – more than doubling the number of regions previously identified– and showed what specific genes and pathways they impacted. This will lead to future opportunities to better identify people who are likely to develop the condition, as well as advancing research on improved treatments.

Associate Professor Jan Fullerton, who is a Senior Research Scientist at NeuRA and a Conjoint Associate Professor at UNSW, said more clearly identifying the genetic signatures that are associated with BD creates exciting opportunities for future research.

“Your genome is a book made up of letters, sentences and paragraphs that tell part of your personal story. This study is looking at common spelling mistakes that can change the meaning of the story, and occur more frequently in people with BD. If a person’s genome has enough spelling mistakes, then this can increase their risk of BD,” said A/Prof. Fullerton.

Results from the study have also revealed the biological pathways that are impacted in BD, including targets of medicines used to treat BD and other conditions, which may lead to the development of more targeted medications, or the repurposing of existing medications as potential BD treatments.

“If we can identify the genetic risk factors for bipolar, we are more able to understand the biology of the disorder, and with hope, better treat it,” A/Prof. Fullerton said.

“Insights from this piece of work will help to develop personalised medicine to improve quality of life for people living with BD, and potentially prediction and prevention of bipolar symptoms.”

Researchers studied over 7.5 million common variations in the DNA sequence, finding that nearly 8600 common variations explain the majority of risk attributed to this particular class of genetic variation, but there is yet more to discover in the genome to fully explain genetic risk.

“This study looked at the common single-letter spelling mistakes in the genome story book, but was not able to examine instances where whole sentences are deleted, paragraphs are reversed, or pages are duplicated,” A/Prof. Fullerton said.

“Excitingly, we seem to be at an inflection point in genome discovery for bipolar at present – and with continued collaborative efforts, we will see a dramatic increase in genetic findings in the coming years.”

 

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