Moons Tim, De Hert Marc, Gellens Edith, Gielen Leen, Sweers Kim, Jacqmaert Sigrun, van Winkel Ruud, Vandekerckhove Philippe, Claes Stephan
GRASP research group, UPC KULeuven, Campus Leuven, Leuven, Belgium.
UPC KULeuven, campus Kortenberg, Kortenberg, Belgium.
PLoS One. 2016 Mar 30;11(3):e0150464. doi: 10.1371/journal.pone.0150464. eCollection 2016.
Schizophrenia is a genetically heterogeneous disorder that is associated with several common and rare genetic variants. As technology involved, cost advantages of chip based genotyping was combined with information about rare variants, resulting in the Infinium HumanExome Beadchip. Using this chip, a sample of 493 patients with schizophrenia or schizoaffective disorder and 484 healthy controls was genotyped.
From the initial 242901 SNVs, 88306 had at least one minor allele and passed quality control. No variant reached genomewide-significant results (p<10(-8)). The SNP with the lowest p-value was rs1230345 in WISP3 (p = 3.0510(-6)), followed by rs9311525 in CACNA2D3 (p = 1.0310(-5)) and rs1558557 (p = 3.85*10(-05)) on chromosome 7. At the gene level, 3 genes were of interest: WISP3, on chromosome 6q21, a signally protein from the extracellular matrix. A second candidate gene is CACNA2D3, a regulator of the intracerebral calcium pathway. A third gene is TNFSF10, associated with p53 mediated apoptosis.
精神分裂症是一种具有遗传异质性的疾病，与多种常见和罕见的基因变异相关。随着技术的发展，基于芯片的基因分型的成本优势与关于罕见变异的信息相结合，产生了Infinium HumanExome Beadchip芯片。使用该芯片，对493例精神分裂症或分裂情感性障碍患者和484例健康对照的样本进行了基因分型。
在最初的242901个单核苷酸变异（SNV）中，88306个至少有一个次要等位基因并通过了质量控制。没有变异达到全基因组显著结果（p<10^(-8)）。p值最低的单核苷酸多态性（SNP）是WISP3基因中的rs1230345（p = 3.05×10^(-6)），其次是CACNA2D3基因中的rs9311525（p = 1.03×10^(-5)）以及7号染色体上的rs1558557（p = 3.85×10^(-5)）。在基因水平上，有3个基因值得关注：位于6q21染色体上的WISP3，一种来自细胞外基质的信号蛋白。第二个候选基因是CACNA2D3，一种脑内钙途径的调节因子。第三个基因是TNFSF10，与p53介导的细胞凋亡相关。
