Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an Jiaotong University, Xi'an 710061, China.
School of Medicine & Forensics, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Eur Psychiatry. 2020 Feb 20;63(1):e17. doi: 10.1192/j.eurpsy.2019.6.
Psychiatric disorders are a group of complex psychological syndromes with high prevalence. Recent studies observed associations between altered plasma proteins and psychiatric disorders. This study aims to systematically explore the potential genetic relationships between five major psychiatric disorders and more than 3,000 plasma proteins.
The genome-wide association study (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) were driven from the Psychiatric GWAS Consortium. The GWAS datasets of 3,283 human plasma proteins were derived from recently published study, including 3,301 study subjects. Linkage disequilibrium score (LDSC) regression analysis were conducted to evaluate the genetic correlations between psychiatric disorders and each of the 3,283 plasma proteins.
LDSC observed several genetic correlations between plasma proteins and psychiatric disorders, such as ADHD and lysosomal Pro-X carboxypeptidase (p value = 0.015), ASD and extracellular superoxide dismutase (Cu-Zn; p value = 0.023), BD and alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (p value = 0.007), MDD and trefoil factor 1 (p value = 0.011), and SCZ and insulin-like growth factor-binding protein 6 (p value = 0.011). Additionally, we detected four common plasma proteins showing correlation evidence with both BD and SCZ, such as tumor necrosis factor receptor superfamily member 1B (p value = 0.012 for BD, p value = 0.011 for SCZ).
This study provided an atlas of genetic correlations between psychiatric disorders and plasma proteome, providing novel clues for pathogenetic and biomarkers, therapeutic studies of psychiatric disorders.
精神障碍是一组具有高患病率的复杂心理综合征。最近的研究观察到改变的血浆蛋白与精神障碍之间存在关联。本研究旨在系统地探讨五种主要精神障碍与 3000 多种血浆蛋白之间潜在的遗传关系。
从精神疾病 GWAS 联盟获得注意力缺陷/多动障碍 (ADHD)、自闭症谱系障碍 (ASD)、双相情感障碍 (BD)、精神分裂症 (SCZ) 和重度抑郁症 (MDD) 的全基因组关联研究 (GWAS) 数据集。3283 个人类血浆蛋白的 GWAS 数据集来源于最近发表的研究，包括 3301 个研究对象。连锁不平衡得分 (LDSC) 回归分析用于评估精神障碍与 3283 种血浆蛋白中的每一种之间的遗传相关性。
LDSC 观察到血浆蛋白与精神障碍之间存在几种遗传相关性，例如 ADHD 与溶酶体 Pro-X 羧肽酶 (p 值=0.015)、ASD 与细胞外超氧化物歧化酶 (Cu-Zn;p 值=0.023)、BD 与α-N-乙酰半乳糖胺-α-2,6-唾液酸转移酶 6 (p 值=0.007)、MDD 与三叶因子 1 (p 值=0.011)和 SCZ 与胰岛素样生长因子结合蛋白 6 (p 值=0.011)。此外，我们还检测到四种常见的血浆蛋白与 BD 和 SCZ 均具有相关性证据，例如肿瘤坏死因子受体超家族成员 1B (BD 的 p 值=0.012，SCZ 的 p 值=0.011)。
本研究提供了精神障碍与血浆蛋白质组之间遗传相关性的图谱，为精神障碍的发病机制和生物标志物、治疗研究提供了新的线索。
