A two-stage association study suggests BRAP as a susceptibility gene for schizophrenia.
A two-stage association study suggests BRAP as a susceptibility gene for schizophrenia.
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DOI：
10.1371/journal.pone.0086037
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Zhang F;Liu C;Xu Y;Qi G;Yuan G;Cheng Z;Wang J;Wang G;Wang Z;Zhu W;Zhou Z;Zhao X;Tian L;Jin C;Yuan J;Zhang G;Chen Y;Wang L;Lu T;Yan H;Ruan Y;Yue W;Zhang D
精神分裂症（SZ）是一种神经发育障碍，免疫功能改变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激活的蛋白激酶级联和炎症信号传导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，我们进行了一项两阶段的研究，以研究汉族人群中BRAP多态性与SZ的关系。在第一阶段，我们从GWAS数据中筛选BRAP中的snp，检测到三个相关snp，其中rs3782886是最显著的一个（P = 2.31E-6, OR = 0.67）。在第二阶段，我们在独立收集的人群中验证了这三个snp，包括1957例患者和1509例对照，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) mRNA水平相关（P < 1.0E-4）。我们的数据表明，BRAP基因可能赋予中国汉族人群SZ易感性，进一步证明了该疾病与发育和/或神经炎症级联反应有关。
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.
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影响因子：
4.5
作者：
Avery CL;He Q;North KE;Ambite JL;Boerwinkle E;Fornage M;Hindorff LA;Kooperberg C;Meigs JB;Pankow JS;Pendergrass SA;Psaty BM;Ritchie MD;Rotter JI;Taylor KD;Wilkens LR;Heiss G;Lin DY
通讯作者：
Lin DY
DOI：
10.1192/bjp.bp.110.084384
发表时间：
2011-03
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Owen MJ;O'Donovan MC;Thapar A;Craddock N
通讯作者：
Craddock N
影响因子：
14.9
作者：
Lee, Phil Hyoun;Shatkay, Hagit
通讯作者：
Shatkay, Hagit
影响因子：
4.5
作者：
Stranger BE;Montgomery SB;Dimas AS;Parts L;Stegle O;Ingle CE;Sekowska M;Smith GD;Evans D;Gutierrez-Arcelus M;Price A;Raj T;Nisbett J;Nica AC;Beazley C;Durbin R;Deloukas P;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
5.8
作者：
Lee, Phil Hyoun;Shatkay, Hagit
通讯作者：
Shatkay, Hagit