Jung Jin Young, Ahn Yeeun, Park Jung-Wook, Jung Kyeongmin, Kim Soyeon, Lim Soohyun, Jung Sang-Hyuk, Kim Hyejin, Kim Beomsu, Hwang Mi Yeong, Kim Young Jin, Park Woong-Yang, Okbay Aysu, O'Connell Kevin S, Andreassen Ole A, Myung Woojae, Won Hong-Hee
Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
Nat Hum Behav. 2025 Apr 14. doi: 10.1038/s41562-025-02155-z.
Subjective well-being (SWB) is important for understanding human behaviour and health. Although the connection between SWB and psychiatric disorders has been studied, common genetic mechanisms remain unclear. This study aimed to explore the genetic relationship between SWB and psychiatric disorders. Bivariate causal mixture modelling (MiXeR), polygenic risk score (PRS) and Mendelian randomization (MR) analyses showed substantial polygenic overlap and associations between SWB and the psychiatric disorders. Subsequent replication studies in East Asian populations confirmed the polygenic overlap between schizophrenia and SWB. The conditional and conjunctional false discovery rate analyses identified additional or shared genetic loci associated with SWB or psychiatric disorders. Functional annotation revealed enrichment of specific brain tissues and genes associated with SWB. The identified genetic loci showed cross-ancestry transferability between the European and Korean populations. Our findings provide valuable insights into the common genetic mechanisms underlying SWB and psychiatric disorders.
主观幸福感（SWB）对于理解人类行为和健康至关重要。尽管已经对主观幸福感与精神障碍之间的联系进行了研究，但共同的遗传机制仍不清楚。本研究旨在探讨主观幸福感与精神障碍之间的遗传关系。双变量因果混合模型（MiXeR）、多基因风险评分（PRS）和孟德尔随机化（MR）分析表明，主观幸福感与精神障碍之间存在大量多基因重叠和关联。随后在东亚人群中的重复研究证实了精神分裂症与主观幸福感之间的多基因重叠。条件和联合错误发现率分析确定了与主观幸福感或精神障碍相关的其他或共享遗传位点。功能注释揭示了与主观幸福感相关的特定脑组织和基因的富集。所确定的遗传位点在欧洲和韩国人群之间显示出跨祖先的可转移性。我们的研究结果为深入了解主观幸福感和精神障碍背后的共同遗传机制提供了有价值的见解。
