Evaluating the heterogeneous treatment effects of major depression polygenic risk scores on self-harm using causal forest.
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| Title: | Evaluating the heterogeneous treatment effects of major depression polygenic risk scores on self-harm using causal forest. |
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| Authors: | Jeong, Eunji (AUTHOR), Lee, Chanhui (AUTHOR), Kim, Hyejin (AUTHOR), Yu, Hyeona (AUTHOR), Lee, Jakyung (AUTHOR), Ha, Tae Hyon (AUTHOR), Won, Hong-Hee (AUTHOR), Myung, Woojae (AUTHOR), Kang, Hyo Shin (AUTHOR), Park, Jungkyu (AUTHOR) |
| Source: | Journal of Mental Health. Jun2026, Vol. 35 Issue 3, p330-343. 14p. |
| Subjects: | Self-injurious behavior, T-test (Statistics), Research funding, Europeans, Social factors, Treatment effectiveness, Genetic risk score, Uk Biobank Ltd., Causality (Physics), Data analysis software, Mental depression |
| Abstract: | Background: Self-harm, defined as non-fatal self-inflicted harm regardless of suicidal intent, is a critical global health issue influenced by the interaction between genetic and environmental factors. Aims: This study investigates the causal effect of major depression polygenic risk scores (MD PRS) on self-harm in individuals of European ancestry and explores how environmental and personal factors moderate this effect. Methods: Using data from 91,778 UK Biobank participants, we compared the top 10% with the highest MD PRS (the genetically vulnerable group) against the remainder. The causal relationship was examined using a causal forest approach to estimate average and heterogeneous treatment effects across non-genetic contributors. Results: Higher MD PRS was associated with an increased risk of self-harm. Significant heterogeneity was observed: the association was stronger among individuals exposed to physical violence or partner belittlement, but weaker among older adults and those with higher income. Conclusions: These findings highlight the importance of personalized prevention. Genetic vulnerability to depression reflects a heightened sensitivity to adverse environments, suggesting that genetic risk should be considered alongside trauma and socioeconomic contexts. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Background: Self-harm, defined as non-fatal self-inflicted harm regardless of suicidal intent, is a critical global health issue influenced by the interaction between genetic and environmental factors. Aims: This study investigates the causal effect of major depression polygenic risk scores (MD PRS) on self-harm in individuals of European ancestry and explores how environmental and personal factors moderate this effect. Methods: Using data from 91,778 UK Biobank participants, we compared the top 10% with the highest MD PRS (the genetically vulnerable group) against the remainder. The causal relationship was examined using a causal forest approach to estimate average and heterogeneous treatment effects across non-genetic contributors. Results: Higher MD PRS was associated with an increased risk of self-harm. Significant heterogeneity was observed: the association was stronger among individuals exposed to physical violence or partner belittlement, but weaker among older adults and those with higher income. Conclusions: These findings highlight the importance of personalized prevention. Genetic vulnerability to depression reflects a heightened sensitivity to adverse environments, suggesting that genetic risk should be considered alongside trauma and socioeconomic contexts. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 09638237 |
| DOI: | 10.1080/09638237.2026.2645539 |
