Genetic Roots of Depression Reveal Strong Suicide Risk Signals

Summary: New research shows that depression beginning before age 25 has a much stronger hereditary component than depression that emerges later in life. By analyzing genetic data from over 150,000 people with depression, researchers identified distinct genetic regions linked specifically to early-onset cases.

Individuals with high genetic risk for early-onset depression were twice as likely to attempt suicide within a decade. The findings highlight a critical window for early intervention and suggest that genetics could eventually guide personalized suicide-prevention strategies.

Key Facts

  • Early Genetic Risk: Depression before age 25 shows stronger genetic influence than late-onset cases.
  • Higher Suicide Probability: One in four individuals with high early-onset genetic risk attempted suicide within 10 years.
  • Distinct Gene Regions: Twelve genetic regions were linked to early-onset depression, compared with two for late-onset cases.

Source: Karolinska Institute

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.

Funding: 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.

Key Questions Answered:

Q: What did researchers discover about early-onset depression?

A: Depression beginning before age 25 has stronger genetic influences and carries a higher risk of suicide attempts than depression occurring later in life.

Q: How does genetic risk relate to suicide attempts?

A: Individuals with a high genetic risk for early-onset depression were twice as likely to attempt suicide within 10 years compared to those with low genetic risk.

Q: Why does this study matter for treatment?

A: The findings support precision psychiatry—suggesting genetic profiling may help clinicians identify high-risk individuals who need intensified monitoring and prevention.

Editorial Notes:
– This article was written by a Neuroscience News editor.
– Journal paper reviewed in full.
– Additional context added by our staff.

About this genetics and mental health research news

Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is credited to Neuroscience News

Original Research: Open access.
Genome-wide association analyses identify distinct genetics architectures for early-onset and late- onset depression” by Lu Yi et al. Nature Genetics


Abstract

Genome-wide association analyses identify distinct genetics architectures for early-onset and late- onset depression

Major depressive disorder (MDD) is a common and heterogeneous disorder of complex etiology.

Studying more homogeneous groups stratified according to clinical characteristics, such as age of onset, can improve the identification of the underlying genetic causes and lead to more targeted treatment strategies.

We leveraged Nordic biobanks with longitudinal health registries to investigate differences in the genetic architectures of early-onset (eoMDD; n = 46,708 cases) and late-onset (loMDD; n = 37,168 cases) MDD.

We identified 12 genomic loci for eoMDD and two for loMDD. Overall, the two MDD subtypes correlated moderately (genetic correlation, rg = 0.58) and differed in their genetic correlations with related traits.

These findings suggest that eoMDD and loMDD have partially distinct genetic signatures, with a specific developmental brain signature for eoMDD.

Importantly, we demonstrate that polygenic risk scores (PRS) for eoMDD predict suicide attempts within the first 10 years after the initial diagnosis: the absolute risk for suicide attempt was 26% in the top PRS decile, compared to 12% and 20% in the bottom decile and the intermediate group, respectively.

Taken together, our findings can inform precision psychiatry approaches for MDD.