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首页> 外文期刊>Psychiatric genetics >Association of DISC1 gene with schizophrenia in families from two distinct French and Algerian populations.
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Association of DISC1 gene with schizophrenia in families from two distinct French and Algerian populations.

机译：在来自两个不同的法国和阿尔及利亚人群的家庭中，DISC1基因与精神分裂症的关联。

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OBJECTIVE: The Disrupted-in-Schizophrenia-1 (DISC1) gene is a promising genetic risk factor for major mental illnesses, especially schizophrenia. Several variants encompassing the DISC1 gene have been associated with schizophrenia and specific clinical features. Negative results were nevertheless observed, stratification biases, heterogeneity of the analyzed samples and low statistical power being potentially involved. METHODS: We analyzed four single nucleotide polymorphisms (SNPs), including three non-synonymous SNPs, of DISC1 in two independent samples of trios, from France and Algeria, using family-based association tests to elude statistical limits. RESULTS: In 114 French schizophrenia trios, the C allele of non-synonymous rs6675281/Leu607Phe/C1872T was significantly over-transmitted [odds ratio (OR)=2.3, 95% confidence interval (CI)=1.1-4.4]. This same SNP was also more frequently transmitted in the 100 Algerian schizophrenia trios (OR=2.6, 95% CI=0.9-7.3). In the combined 214 trios, a significant over-transmission of the C allele of rs6675281 to the affected probands was observed (P=0.002), even after correction for multiple testing (P corrected=0.01 OR=2.4 and 95% CI=1.3-4.2). Assessing if a dimension of schizophrenia could be more specifically involved, we found that patients with the C allele had a significantly higher Scale for the Assessment of Negative Symptoms total score (P=0.0002). CONCLUSION: The analysis adds convergent evidence in favor of a significant role of the DISC1 gene as a risk factor for schizophrenia, as present in two different samples, in family trios rather than with a case--control approach, and even when multiple tests are controlled for. We could further potentially attribute this effect to the negative dimension of schizophrenia.
机译：目的：精神分裂症1基因（DISC1）是重大精神疾病尤其是精神分裂症的一种有前途的遗传危险因素。包含DISC1基因的几种变体与精神分裂症和特定的临床特征有关。然而，观察到阴性结果，可能涉及分层偏差，分析样品的异质性和低统计能力。方法：我们使用基于家族的关联测试来分析统计上的差异，对来自法国和阿尔及利亚的两个三重奏独立样本中的DISC1的四个单核苷酸多态性（SNP），包括三个非同义SNP，进行了分析。结果：在114例法国精神分裂症三重症患者中，非同义rs6675281 / Leu607Phe / C1872T的C等位基因显着超标[比值比（OR）= 2.3，95％置信区间（CI）= 1.1-4.4]。同样的SNP在100个阿尔及利亚精神分裂症三重症患者中也更常见（OR = 2.6，95％CI = 0.9-7.3）。在组合的214个三重奏中，即使经过多次测试的校正（P校正= 0.01 OR = 2.4和95％CI = 1.3-，校正后）仍观察到rs6675281的C等位基因向受影响的先证者的过度过量传播（P = 0.002）。 4.2）。评估是否可以更具体地涉及精神分裂症的维度，我们发现C等位基因患者的阴性症状总评分量表明显更高（P = 0.0002）。结论：该分析增加了趋同性证据，证明DISC1基因作为精神分裂症的危险因素具有重要作用，正如在两个不同样品中，家庭三重奏中所采用的那样，而不是采用病例对照方法，甚至当进行多重检测时也是如此。控制。我们可以进一步将这种影响归因于精神分裂症的负面影响。

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