In what is the largest study thus far of the genetic risk of depression, researchers from Aarhus University have worked with other institutions on identifying several new genes for depression. The discovery is a step on the road to developing a more targeted and effective treatment of depression.

2018.05.03 | Helle Horskjær Hansen

The genetic basis for depression overlaps other psychiatric disorders such as bipolar disorder and schizophrenia. Six of the genes that have been identified are also associated with schizophrenia. Photo: Colourbox

A new genome-wide analysis of more than 135,000 people with major depression has identified 44 genomic variants significantly associated with depression – of which 30 are newly discovered. This provides hope to the around 500,000 Danes affected by a disease that has been described as one of the biggest public health issues in the world.

This is because – despite decades of research in the field – insights into the disease's biological mechanisms have so far been inadequate. With consequences for the development of treatment to follow.   

What can the new genetic discoveries be used for?

"The genomic variants and risk genes that have been identified open completely new windows into studying and understanding the underlying biology", says one of the co-leaders of the study, Anders Børglum from the Department of Biomedicine, Aarhus University, and the national psychiatry research project iPSYCH.

Antidepressant drugs have a limited effect and not everyone who suffers from major depression benefits from the treatment being offered today. 

"It’s therefore very important to understand more about the biological disease mechanisms which can uncover targets for new medical treatment," says Anders Børglum before continuing: 

"The results show that molecular targets of known antidepressant drugs are enriched in the genetic findings, which further reinforces the hope that the identified risk genes can point towards new molecular targets for treatment. We’re on the right track.”

The study is the largest of its kind so far, involving over 200 researchers who have joined forces in the international collaboration Psychiatric Genomics Consortium. The Danish iPSYCH project contributes with results from a study of the largest group of people diagnosed with major depression in the study. The results of the study have just been published in the scientific journal Nature Genetics.

Treatment tailored to genetic profiles

Anders Børglum hopes that the discoveries can provide impetus for the development of personalised medicine, for example by using a genetic profile to help tailor treatment to the individual patient.

"We show – in the Danish study among others – that people who have recurrent episodes of depression have a greater burden of genetic risk variants than those who only suffer a single depression. The same is true for those people who are diagnosed with depression early in life. Perhaps we should therefore be particularly attentive and active in the treatment of people with depression who have greater genetic vulnerability."

The study also shows that we are all carriers of numerous genetic variants for depression, but people who have a particularly large number of these genes have a greater vulnerability and are prone to suffer from more severe depression.

"We know that many non-genetic factors also contribute to the risk of being affected by depression. For depression, the heritability is approximately 40 per cent, meaning that environmental factors thus constitute the bulk of the contributory causes. By identifying the genetic factors, we’re getting new tools for research into the interplay between genetics and the environment, so that we can gain a more complete understanding of the disease mechanisms," explains Anders Børglum.

Background for the results:

• The study is a meta-analysis of more than 135,000 people with depression and 344,000 people in the control group.
• The study is a collaboration between researchers from 161 institutions around the world in the Psychiatric Genomics Consortium.
• The Danish integrative psychiatric research project iPSYCH contributes with results from the largest single study of people with diagnosed depression.
• The study has been financed by (among others): The Lundbeck Foundation, Denmark; the US National Institute of Mental Health and the National Institute of Drug Abuse; the Dutch scientific organisation; the Federal Ministry of Education and Research, Germany; the Swedish Research Council; and the National Health and Medical Research Council, Australia.
• The results of the study have been published in the article ”Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression” in Nature Genetics.