Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects
Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects
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DOI：
10.1016/j.biopsych.2016.08.014
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发表时间：
2017-07-15
影响因子：
10.6
通讯作者：
Kirov, George
中科院分区：
文献类型：
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作者：
Kendall, Kimberley M.;Rees, Elliott;Kirov, George
背景：英国生物银行是生物医学研究的独特资源，拥有来自普通人群的50万成年人的广泛表型和遗传数据。我们的目的是研究神经发育拷贝数变异（CNVs）对参与者认知表现的影响。方法：使用Affymetrix Power Tools和PennCNV-Affy软件对首批152,728名基因分型个体的Affymetrix微阵列进行分析。我们标注了93个CNVs的列表，并将其频率与对照数据集进行了比较。我们分析了12名与精神分裂症相关的CNVs携带者（n = 1087）和另外41名神经发育性CNVs携带者（n = 484）在7项认知测试中的表现。结果：生物库受试者中93个CNVs的频率与来自其他数据集的26,628名对照受试者的频率非常相似。精神分裂症相关CNVs携带者和41组其他神经发育性CNVs携带者在认知测试中的表现受损，14个比较中有9个在多次测试校正后仍具有统计学显著性。他们的教育和职业成就也较低（p值在10（-7）和10（-18）之间）。与生物库中的精神分裂症患者相比，认知能力的缺陷是适度的（Z分数下降在0.01到0.51之间）（Z分数下降在0.35到0.90之间）。结论：这是迄今为止最大的CNVs认知表型研究。来自一般人群的神经发育性CNVs的成年携带者有显著的认知缺陷。英国生物银行将为进一步分析CNVs的表型后果提供前所未有的机会。
BACKGROUND: The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population. We aimed to examine the effect of neuro-developmental copy number variants (CNVs) on the cognitive performance of participants.METHODS: We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. We annotated a list of 93 CNVs and compared their frequencies with control datasets. We analyzed the performance on seven cognitive tests of carriers of 12 CNVs associated with schizophrenia (n = 1087) and of carriers of another 41 neurodevelopmental CNVs (n = 484).RESULTS: The frequencies of the 93 CNVs in the Biobank subjects were remarkably similar to those among 26,628 control subjects from other datasets. Carriers of schizophrenia-associated CNVs and of the group of 41 other neurodevelopmental CNVs had impaired performance on the cognitive tests, with nine of 14 comparisons remaining statistically significant after correction for multiple testing. They also had lower educational and occupational attainment (p values between 10(-7) and 10(-18)). The deficits in cognitive performance were modest (Z score reductions between 0.01 and 0.51), compared with individuals with schizophrenia in the Biobank (Z score reductions between 0.35 and 0.90).CONCLUSIONS: This is the largest study on the cognitive phenotypes of CNVs to date. Adult carriers of neurodevelopmental CNVs from the general population have significant cognitive deficits. The UK Biobank will allow unprecedented opportunities for analysis of further phenotypic consequences of CNVs.