Department of Neurology, The First Affiliated Hospital of Anhui Medical University. Hefei, Anhui, 230001, China.
Collaborative Innovation Center of Bone and Immunology between Sihong Hospital and Soochow University, Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, China.
J Affect Disord. 2024 Nov 15;365:534-541. doi: 10.1016/j.jad.2024.08.149. Epub 2024 Aug 24.
Antisocial behavior (ASB) infringes on the rights of others and significantly disrupts social order. Studies have shown that ASB is phenotypically associated with various psychiatric disorders. However, these studies often neglected the importance of genetic foundations.
This study utilized genome-wide association studies and pleiotropy analysis to explore the genetic correlation between ASB and psychiatric disorders. Linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods were employed to assess genetic correlations, and the PLACO method was used for pleiotropy analysis. Functional annotation and biological pathway analysis of identified pleiotropic genes were performed using enrichment analysis. Furthermore, Mendelian randomization (MR) analysis was conducted to validate these causal relationships.
LDSC and HDL analysis showed that significant positive genetic correlations were between ASB and attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Multiple potential pleiotropic genetic loci were identified, particularly the FOXP2 and MDFIC genes located at the 7q31.1 locus. Enrichment analysis showed that these pleiotropic genes are highly expressed in several brain regions (such as the hypothalamus, cerebellar hemisphere, cortex, and amygdala) and immune-related cells. MR analysis further confirmed the causal effects ADHD, SCZ, and MDD on ASB risk.
This study reveals significant genetic correlations and potential causal mechanisms between ASB and various psychiatric disorders. The MR analysis confirmed the causal effects of psychiatric disorders on ASB. These findings deepen our understanding of the genetic architecture of psychiatric disorders and ASB.
反社会行为（ASB）侵犯他人权利，严重扰乱社会秩序。研究表明，ASB 在表型上与各种精神障碍有关。然而，这些研究往往忽略了遗传基础的重要性。
本研究利用全基因组关联研究和多效性分析来探讨 ASB 与精神障碍之间的遗传相关性。使用连锁不平衡评分回归（LDSC）和高清晰度（HDL）方法评估遗传相关性，并使用 PLACO 方法进行多效性分析。使用富集分析对鉴定出的多效性基因进行功能注释和生物途径分析。此外，还进行了孟德尔随机化（MR）分析来验证这些因果关系。
LDSC 和 HDL 分析表明，ASB 与注意缺陷多动障碍（ADHD）、精神分裂症（SCZ）、重度抑郁症（MDD）和创伤后应激障碍（PTSD）之间存在显著的正遗传相关性。确定了多个潜在的多效性遗传位点，特别是位于 7q31.1 位置的 FOXP2 和 MDFIC 基因。富集分析表明，这些多效性基因在几个大脑区域（如下丘脑、小脑半球、皮质和杏仁核）和免疫相关细胞中高度表达。MR 分析进一步证实了 ADHD、SCZ 和 MDD 对 ASB 风险的因果影响。
本研究揭示了 ASB 与各种精神障碍之间存在显著的遗传相关性和潜在的因果机制。MR 分析证实了精神障碍对 ASB 的因果影响。这些发现加深了我们对精神障碍和 ASB 遗传结构的理解。
