Strong association of de novo copy number mutations with sporadic schizophrenia
Strong association of de novo copy number mutations with sporadic schizophrenia
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DOI：
10.1038/ng.162
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发表时间：
2008-07-01
期刊：
影响因子：
30.8
通讯作者：
Karayiorgou, Maria
中科院分区：
文献类型：
--
作者：
Xu, Bin;Roos, J. Louw;Karayiorgou, Maria
精神分裂症是一种病因不同的精神疾病，以家族性和非家族性(散发性)形式存在[1]。在这里，我们研究了具有相对高外显性的罕见新拷贝数(CN)突变对精神分裂症遗传成分的贡献的可能性。我们进行了全基因组扫描，并实施了一系列步骤来发现和确认CN突变。已证实的从头基因突变与精神分裂症显著相关(P=0.00078)，在散发性(但不是家族性)精神分裂症患者中，其总体相似程度是未受影响的对照组的8倍。相比之下，罕见的遗传性CN突变仅在零星病例中略有增加。我们的结果表明，罕见的新胚系突变导致了散发性精神分裂症的易感性，许多不同基因座的罕见遗传损伤可以至少部分解释这种疾病的遗传异质性。
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms(1). Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively similar to 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.