Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function
Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function
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DOI：
10.1016/j.jpsychires.2011.11.001
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发表时间：
2012-02-01
影响因子：
4.8
通讯作者：
Andreassen, Ole A.
中科院分区：
文献类型：
--
作者：
LeBlanc, Marissa;Kulle, Bettina;Andreassen, Ole A.
背景资料：神经认知功能的几个方面具有高遗传性，但神经认知的分子遗传机制尚不清楚。我们进行了全基因组关联研究（GWAS），以确定与neurocognition.Methods相关的基因：700主题（精神分裂症谱系障碍，n = 190，双相情感障碍是= 157和健康个体n = 353）进行了测试，广泛的神经心理测试电池，和基因型使用的Affyphony全基因组人类SNP阵列6.0。质量控制后，对24项认知测试中的每一项进行SNP剂量的线性回归分析，包括年龄、性别、教育和疾病组作为协变量。此外，还考虑了9个具有全基因组意义的SNP进行上位性相互作用。结果：识别出4个具有全基因组意义的SNP和2个独立的关联信号。PTPRO中的三个内含子SNP与学习和记忆（CVLT-II LDFR）相关（rs 17222089，p = 1.55 x 10（-8）; rs 11056571，p = 1.68 x 10（-8）;和rs 2300290，p = 1.09 x 10（-8））。WDR 72下游的rs719714与执行功能相关（CW-3：抑制，D-KEFS）（p = 4.32 x 10 - 8）。在Grooved Pegboard测试中发现FOXQ 1上游的rs 9378605和SUMO 1 P1下游的rs 11699311之间存在高度显著的上位性相互作用（p = 7.6 x 10（-14））。这些发现应该在独立样本中重复，但表明PTPRO在学习和记忆中的作用，WDR 72与执行功能，以及FOXQ 1和SUMO 1 P1之间的相互作用对心理速度的影响。(C)2011爱思唯尔有限公司版权所有。
Background: Several aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition.Methods: 700 Subjects (schizophrenia spectrum disorder, n = 190, bipolar disorder is = 157 and healthy individuals n = 353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions.Results: Four SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p = 1.55 x 10(-8); rs11056571, p = 1.68 x 10(-8); and rs2300290, p = 1.09 x 10(-8)). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p = 4.32 x 10(-8)). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p = 7.6 x 10(-14)).Conclusions: We identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed. (C) 2011 Elsevier Ltd. All rights reserved.