Liu Ping, Luo Xinqun, Cao Liping, Zhang Yong, Ji Jiawu, Wang Xiaoping, Wang Kesheng, Pan Xinghua, Yang Ruilan, Tan Zewen, Tan Yunlong, Li Chiang-Shan, Guo Xiaoyun, Wang Zhiren, Luo Xingguang
Department of Psychosomatic Medicine, People's Hospital of Deyang City, Deyang, Sichuan, China.
Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Front Psychiatry. 2025 Jan 20;15:1420395. doi: 10.3389/fpsyt.2024.1420395. eCollection 2024.
has been associated with alcoholism, bipolar disorder and autism, but the comparability and specificity issues of the findings remain unaddressed. The present study aimed to comprehensively analyze various neuropsychiatric disorders pinpoint the most reliable conditions predisposed by .
A total of 2,187 imputed SNPs across were examined in 1,167,439 subjects from 72 independent cohorts with 18 different neuropsychiatric disorders. SNP-disease associations were tested and then meta-analyzed, followed by FDR correction, to identify significant disease-risk SNPs. Finally, functional studies on the differential mRNA expression in brains and the potential regulatory effects of disease-risk alleles on mRNA expression, gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA) and average thickness (TH) were conducted.
In European descent, alcoholism was most significantly associated with variants (245 SNPs with 5.5×10≤p ≤ 0.049 and 4.9×10≤q ≤ 0.034) that were largely shared across cocaine dependence, marijuana dependence, nicotine dependence, polysubstance dependence, schizophrenia, OCD, and autism (8.2×10≤p ≤ 0.050 and 1.9×10≤q ≤ 0.049); in Chinese population, bipolar disorder was also significantly associated with variants (10 SNPs: 1.3×10≤p ≤ 4.7×10 and 0.025≤q ≤ 0.031). Furthermore, the disease-risk alleles had highly similar regulatory effects on mRNA expression (8.1×10≤p ≤ 0.046), subcortical GMVs (7.0×10≤p ≤ 0.048) and cortical TH and SA (1.3×10≤p ≤ 0.050) in brains across alcoholism, schizophrenia, OCD and autism. The bipolar disorder-risk alleles had these regulatory effects but with different effect patterns. Finally, mRNA was differentially expressed in several brain regions between alcoholism or schizophrenia and controls.
is primarily linked to substance use disorders, schizophrenia, OCD, autism and bipolar disorder, not only statistically but also biologically.
已发现其与酒精中毒、双相情感障碍和自闭症有关，但研究结果的可比性和特异性问题仍未得到解决。本研究旨在全面分析各种神经精神疾病，找出由其引发的最可靠的相关病症。
在来自72个独立队列的1,167,439名患有18种不同神经精神疾病的受试者中，对总共2187个估算的单核苷酸多态性（SNPs）进行了检测。对SNP与疾病的关联进行了测试，然后进行荟萃分析，接着进行错误发现率（FDR）校正，以确定显著的疾病风险SNP。最后，对大脑中差异mRNA表达以及疾病风险等位基因对mRNA表达、皮质下结构的灰质体积（GMV）、皮质表面积（SA）和平均厚度（TH）的潜在调节作用进行了功能研究。
在欧洲血统人群中，酒精中毒与该变异最为显著相关（245个SNP，5.5×10≤p≤0.049且4.9×10≤q≤0.034），这些变异在很大程度上也存在于可卡因依赖、大麻依赖、尼古丁依赖、多种物质依赖、精神分裂症、强迫症和自闭症中（8.2×10≤p≤0.050且1.9×10≤q≤0.049）；在中国人群中，双相情感障碍也与该变异显著相关（10个SNP：1.3×10≤p≤4.7×10且0.025≤q≤0.031）。此外，疾病风险等位基因对酒精中毒、精神分裂症、强迫症和自闭症患者大脑中的mRNA表达（8.1×10≤p≤0.046）、皮质下GMV（7.0×10≤p≤0.048）以及皮质TH和SA（1.3×10≤p≤0.050）具有高度相似的调节作用。双相情感障碍风险等位基因也有这些调节作用，但模式不同。最后，酒精中毒或精神分裂症患者与对照组相比，几个脑区的mRNA表达存在差异。
该基因不仅在统计学上，而且在生物学上主要与物质使用障碍、精神分裂症、强迫症、自闭症和双相情感障碍有关。
