Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China ; Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
PLoS One. 2014 Jan 15;9(1):e86037. doi: 10.1371/journal.pone.0086037. eCollection 2014.
Schizophrenia (SZ) is a neurodevelopmental disorder in which altered immune function typically plays an important role in mediating the effect of environmental insults and regulation of inflammation. The breast cancer suppressor protein associated protein (BRAP) is suggested to exert vital effects in neurodevelopment by modulating the mitogen-activated protein kinase cascade and inflammation signaling. To explore the possible role of BRAP in SZ, we conducted a two-stage study to examine the association of BRAP polymorphisms with SZ in the Han Chinese population. In stage one, we screened SNPs in BRAP from our GWAS data, which detected three associated SNPs, with rs3782886 being the most significant one (P = 2.31E-6, OR = 0.67). In stage two, we validated these three SNPs in an independently collected population including 1957 patients and 1509 controls, supporting the association of rs3782886 with SZ (P = 1.43E-6, OR = 0.73). Furthermore, cis-eQTL analysis indicates that rs3782886 genotypes are associated with mRNA levels of aldehyde dehydrogenase 2 family (ALDH2) (P = 0.0039) and myosin regulatory light chain 2 (MYL2) (P < 1.0E-4). Our data suggest that the BRAP gene may confer vulnerability for SZ in Han Chinese population, adding further evidence for the involvement of developmental and/or neuroinflammatory cascades in the illness.
精神分裂症（SZ）是一种神经发育障碍，其中改变的免疫功能通常在介导环境损伤和炎症调节中起重要作用。乳腺癌抑制蛋白相关蛋白（BRAP）被认为通过调节丝裂原活化蛋白激酶级联和炎症信号在神经发育中发挥重要作用。为了探索 BRAP 在 SZ 中的可能作用，我们进行了两阶段研究，以检查 BRAP 多态性与汉族人群 SZ 的关联。在第一阶段，我们从我们的 GWAS 数据中筛选 BRAP 的 SNPs，检测到三个相关的 SNPs，其中 rs3782886 是最显著的一个（P = 2.31E-6，OR = 0.67）。在第二阶段，我们在一个独立收集的人群中验证了这三个 SNP，包括 1957 名患者和 1509 名对照，支持 rs3782886 与 SZ 的关联（P = 1.43E-6，OR = 0.73）。此外，顺式-eQTL 分析表明，rs3782886 基因型与醛脱氢酶 2 家族（ALDH2）（P = 0.0039）和肌球蛋白调节轻链 2（MYL2）（P < 1.0E-4）的 mRNA 水平相关。我们的数据表明，BRAP 基因可能使汉族人群易患 SZ，为发育和/或神经炎症级联参与疾病提供了进一步的证据。
