Genes may predict suicide risk in depression

Depression in young adulthood has a stronger hereditary component and is associated with a higher risk of suicide attempts than depression that begins later in life, according to a new study published in Nature Genetics by researchers at Karolinska Institutet, among others.

“We hope that genetic information will be able to help healthcare professionals identify people at high risk of suicide, who may need more support and closer follow-up,” says Lu Yi, senior researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and one of the study’s corresponding authors.

Depression is a common mental illness that can affect people at different stages of life. The new study shows that depression that begins before the age of 25 has a stronger hereditary component than depression that begins late in life.

Major genetic differences

The study, based on medical records and genetic data from over 150,000 people with depression and 360,000 controls in Denmark, Sweden, Norway, Finland and Estonia, compared genetics and risk of suicide attempts in people who had their first depression before the age of 25 (early onset) and those diagnosed after the age of 50 (late onset).

The genetic differences between the groups were large. The researchers identified twelve genetic regions that were linked to early onset and two regions that were linked to late onset. One in four people with a high genetic risk of early-onset depression attempted suicide within ten years of diagnosis, which was about twice as many as people with a low genetic risk.

“We show that early-onset depression has partly different genetic causes than depression that affects older individuals and that the risk of suicide attempts is increased,” says Lu Yi. “This is an important step towards precision medicine in psychiatry, where treatment and preventive measures are tailored to each individual.”

Suicide prevention in healthcare

The researchers now plan to investigate how the genetic differences are related to brain development, stress and life experiences, and whether genetic risk profiles can be used in suicide prevention in healthcare.

The study is a collaboration between Karolinska Institutet in Sweden, the University of Oslo, Norway, Copenhagen University Hospital and Roskilde University in Denmark, the University of Tartu in Estonia and the Nordic research network TRYGGVE. It has been funded by, among others, the European Research Council (ERC) and the US National Institute of Mental Health. Some of the authors have collaborations with pharmaceutical companies, but none that are related to the current study. See the scientific article for more information on potential conflicts of interest.

Publication: “Genome-wide association analyses identify distinct genetics architectures for early-onset and late- onset depression”, John R. Shorter, Joëlle A. Pasman, Siim Kurvits, Andreas Jangmo, Joonas Naamanka, Arvid Harder, Espen Hagen, Kaarina Kowalec, Nelli Frilander, Richard Zetterberg, Joeri J. Meijsen, Jesper R. Gådin, Jacob Bergstedt, Ying Xiong, Sara Hägg, Mikael Landén, Christian Rück, John Wallert, Alkistis Skalkidou, Elise Koch, Bayram C. Akdeniz, Oleksandr Frei, FinnGen, Iiris Hovatta, Ted Reichborn-Kjennerud, Thomas M. Werge, Patrick F. Sullivan, Ole A. Andreassen, Martin Tesli, Kelli Lehto, Alfonso Buil & Yi Lu, Nature Genetics, online 13 November 2025, doi : 10.1038/s41588-025-02396-8.