Zheng Xiaojing, Demirci F Yesim, Barmada M Michael, Richardson Gale A, Lopez Oscar L, Sweet Robert A, Kamboh M Ilyas, Feingold Eleanor
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2014 Nov 7;9(11):e111462. doi: 10.1371/journal.pone.0111462. eCollection 2014.
Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis.
流行病学和遗传学研究表明，精神分裂症和自闭症可能存在遗传联系。除了常见的单核苷酸多态性外，最近的数据表明，一些罕见的拷贝数变异（CNV）是这两种疾病的风险因素。由于我们之前发现阿尔茨海默病中的精神分裂症和精神病（AD+P）存在一些遗传风险，因此我们研究了在精神分裂症和自闭症中报道的CNV是否也与AD+P有关。我们使用Illumina HumanOmni1-Quad BeadChip，在先前在自闭症和精神分裂症中确定的7个复发性CNV区域中搜索与AD+P相关的CNV。在440名AD+P患者中的2名中发现了16号染色体16p11.2重复CNV（chr16: 29,554,843-30,105,652），但在136名无精神病的AD患者、593名有中度精神病状态的AD患者或855名非AD个体中未发现。这种重复CNV在AD+P中的频率（0.46%）与先前在精神分裂症中报道的频率（0.46%）相似。使用NanoString nCounter CNV定制代码集进一步验证了这种重复CNV。16p11.2重复与发育迟缓、智力残疾、行为问题、自闭症、精神分裂症（SCZ）和双相情感障碍有关。这两名AD+P患者没有SCZ、双相情感障碍和自闭症的个人病史，也没有任何已确定的家族病史。据我们所知，我们的病例报告首次表明16p11.2重复也与AD+P有关。尽管这种CNV很罕见，但它可能在精神病的发展中起重要作用。
