Zhang Lusi, Lizano Paulo, Guo Bin, Xu Yanxun, Rubin Leah H, Hill S Kristian, Alliey-Rodriguez Ney, Lee Adam M, Wu Baolin, Keedy Sarah K, Tamminga Carol A, Pearlson Godfrey D, Clementz Brett A, Keshavan Matcheri S, Gershon Elliot S, Sweeney John A, Bishop Jeffrey R
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Brain Behav Immun Health. 2022 Apr 8;22:100459. doi: 10.1016/j.bbih.2022.100459. eCollection 2022 Jul.
Cardiometabolic disorders have known inflammatory implications, and peripheral measures of inflammation and cardiometabolic disorders are common in persons with psychotic disorders. Inflammatory signatures are also related to neurobiological and behavioral changes in psychosis. Relationships between systemic inflammation and cardiometabolic genetic risk in persons with psychosis have not been examined. Thirteen peripheral inflammatory markers and genome-wide genotyping were assessed in 122 participants (n = 86 psychosis, n = 36 healthy controls) of European ancestry. Cluster analyses of inflammatory markers classified higher and lower inflammation subgroups. Single-trait genetic risk scores (GRS) were constructed for each participant using previously reported GWAS summary statistics for the following traits: schizophrenia, bipolar disorder, major depressive disorder, coronary artery disease, type-2 diabetes, low-density lipoprotein, high-density lipoprotein, triglycerides, and waist-to-hip ratio. Genetic correlations across traits were quantified. Principal component (PC) analysis of the cardiometabolic GRSs generated six PC loadings used in regression models to examine associations with inflammation markers. Functional module discovery explored biological mechanisms of the inflammation association of cardiometabolic GRS genes. A subgroup of 38% persons with psychotic disorders was characterized with higher inflammation status. These higher inflammation individuals had lower BACS scores ( = 0.038) compared to those with lower inflammation. The first PC of the cardiometabolic GRS matrix was related to higher inflammation status in persons with psychotic disorders (OR = 2.037, = 0.001). Two of eight modules within the functional interaction network of cardiometabolic GRS genes were enriched for immune processes. Cardiometabolic genetic risk may predispose some individuals with psychosis to elevated inflammation which adversely impacts cognition associated with illness.
心血管代谢紊乱具有已知的炎症影响，炎症的外周指标和心血管代谢紊乱在精神障碍患者中很常见。炎症特征也与精神病中的神经生物学和行为变化有关。尚未研究精神病患者全身炎症与心血管代谢遗传风险之间的关系。对122名欧洲血统的参与者（n = 86名精神病患者，n = 36名健康对照）进行了13种外周炎症标志物和全基因组基因分型评估。对炎症标志物进行聚类分析，将炎症较高和较低的亚组分类。使用先前报告的以下性状的全基因组关联研究（GWAS）汇总统计数据为每个参与者构建单性状遗传风险评分（GRS）：精神分裂症、双相情感障碍、重度抑郁症、冠状动脉疾病、2型糖尿病、低密度脂蛋白、高密度脂蛋白、甘油三酯和腰臀比。对各性状之间的遗传相关性进行了量化。对心血管代谢GRS进行主成分（PC）分析，生成六个PC负荷，用于回归模型，以检验与炎症标志物的关联。功能模块发现探索了心血管代谢GRS基因炎症关联的生物学机制。38%的精神病患者亚组具有较高的炎症状态。与炎症较低的个体相比，这些炎症较高的个体的BACS评分较低（P = 0.038）。心血管代谢GRS矩阵的第一个PC与精神病患者较高的炎症状态相关（OR = 2.037，P = 0.001）。心血管代谢GRS基因功能相互作用网络中的八个模块中有两个富含免疫过程。心血管代谢遗传风险可能使一些精神病患者易患炎症升高，这对与疾病相关的认知产生不利影响。
