▎ACHIEVEMENTS

Prof. Po-Hsiu Kuo of NTU’s Department of Public Health and the Institute of Epidemiological and Preventive Medicine contributed to a groundbreaking global study in collaboration with the Psychiatric Genomics Consortium. Researchers from the UK, South Africa, Brazil, Mexico, the United States, Australia, and several Asian countries also participated in the study. Funded by the U.S. NIH, the Wellcome Trust, and the NIHR Maudsley Biomedical Research Centre, the study results were published in Cell on January 14, 2025.

This is the largest and most diverse genetic study of major depression to date. The researchers identified nearly 300 previously unknown genetic variations associated with the condition. Notably, 100 of these variants were discovered through the inclusion of individuals of African, Hispanic, East Asian, and South Asian ancestry. Previous genetic studies on depression had been focused primarily on white populations, raising concerns that treatments based on such research might be less effective for individuals from other ethnic groups, potentially exacerbating health disparities.

In this landmark study, an international team analyzed anonymized genetic data from over five million individuals from 29 countries, with one in four participants representing non-European ancestries—making it the most diverse genetic study of its kind. The researchers identified 700 genetic variations linked to depression risk, nearly half of which were previously unknown, implicating 308 specific genes in the biological pathways underlying depression.

While each genetic variant individually contributes only a marginal increase in depression risk, the cumulative effect of these variants can significantly heighten susceptibility. By incorporating the newly identified variants, the accuracy of genetic risk prediction for depression was enhanced. Notably, these variants are linked to neurons across several brain regions, offering new insights into how depression impacts the brain. The study also disclosed potential new treatment targets. Remarkably, existing drugs for chronic pain and narcolepsy—such as pregabalin and modafinil—could potentially be repurposed for depression treatment. However, further research and clinical trials are required to evaluate their efficacy and safety in individuals with depression.

This pioneering study not only enriches our understanding of the genetic basis of depression but also underscores the critical importance of including diverse populations in genetic research. Such inclusivity is essential for developing effective and equitable treatments for sufferers of depression in all communities.