Gender differences in CNV burden do not confound schizophrenia CNV associations.
Gender differences in CNV burden do not confound schizophrenia CNV associations.
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DOI：
10.1038/srep25986
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发表时间：
2016-05-17
影响因子：
4.6
通讯作者：
Rees E
中科院分区：
文献类型：
--
作者：
Han J;Walters JT;Kirov G;Pocklington A;Escott-Price V;Owen MJ;Holmans P;O'Donovan MC;Rees E
与普通人群相比，在精神分裂症患者中发现了过量的罕见拷贝数变异（CNVs）。据报道，患有神经发育障碍的女性和普通人群中携带的大而罕见的CNV比男性多。鉴于许多精神分裂症数据集在病例和对照组中的性别比例不相等，CNV负担的性别差异可能会影响病例相关CNV负担的估计以及与单个基因座的关联。在13，276例病例和17，863例对照的样本中，我们观察到与男性相比，病例和对照组中女性的大（≥500 Kb），罕见（<1%）CNV少量但显著过量（对照组OR = 1.17，P = 0.0012;病例OR = 1.11，P = 0.045）。11个精神分裂症相关CNVs的负担在女性病例中显著高于男性病例（OR = 1.38，P = 0.0055），但在考虑对照组中CNVs的发生率后，我们发现这些位点赋予的风险没有显著的性别差异。控制性别对特定CNVs和精神分裂症之间的关联的显著性影响可以忽略不计。在这两种情况下和对照组中，女性过量的大CNVs表明女性保护机制存在于有害的CNVs中，其可能超出神经发育表型。
Compared with the general population, an excess of rare copy number variants (CNVs) has been identified in people with schizophrenia. Females with neurodevelopmental disorders and in the general population have been reported to carry more large, rare CNVs than males. Given that many schizophrenia datasets do not have equal gender ratios in cases and controls, sex differences in CNV burden might have impacted on estimates of case-related CNV burden and also on associations to individual loci. In a sample of 13,276 cases and 17,863 controls, we observed a small but significant excess of large (≥500 Kb), rare (<1%) CNVs in females compared with males in both cases and controls (OR = 1.17, P = 0.0012 for controls; OR = 1.11, P = 0.045 for cases). The burden of 11 schizophrenia-associated CNVs was significantly higher in female cases compared with male cases (OR = 1.38, P = 0.0055), but after accounting for the rates of CNVs in controls, we found no significant gender difference in the risk conferred by these loci. Controlling for gender had a negligible effect on the significance of association between specific CNVs and schizophrenia. The female excess of large CNVs in both cases and controls suggests a female protective mechanism exists for deleterious CNVs that may extend beyond neurodevelopmental phenotypes.