Impact of Neuritin 1 (NRN1) Polymorphisms on Fluid Intelligence in Schizophrenia
Impact of Neuritin 1 (NRN1) Polymorphisms on Fluid Intelligence in Schizophrenia
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DOI：
10.1002/ajmg.b.30996
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Jablensky, Assen
中科院分区：
文献类型：
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作者：
Chandler, David;Dragovic, Milan;Jablensky, Assen
Neuritin I（NRN 1）是一个在神经发育和突触可塑性中具有多种作用的活性调节基因，位于6号染色体上的6p 24-p25区间内，先前被鉴定为与以广泛性认知缺陷（CD）为特征的精神分裂症（SZ）亚型相关。我们测试了NRN 1序列变异对SZ的易感性和患者和非精神病对照组的一般认知能力的影响，通过对NRN 1及其侧翼序列的编码区进行重新测序，并对336名SZ患者和172名健康对照个体的19个单核苷酸多态性（SNP）进行基因分型。所有参与者都完成了全面的神经认知评估，包括评估发病前/既往智商和当前智商的测试。Logistic回归分析发现，19个SNPs中的任何一个与SZ或其CD亚型均无显著关联。然而，线性回归分析显示，患者组中多态性rs 1475157和rs 9405890与当前智商显著相关（多重检验校正后P=0.024和P=0.027）。在SZ中，rs 1475157-rs 9405890单倍型揭示了与当前（“流体”）智力的抽象成分（P = 0.0014）以及与病前和当前智力之间的IQ点损失百分比（P = 0.0041）的高度显著关联。校正后对照组的结果不显著。这是第一次分析NRN 1和SZ之间的关联。研究结果表明，NRN 1作为SZ认知功能的修饰剂的作用，对未来研究环境对“流体”智力的发展和维持的影响具有影响。(C)2009 Wiley-Liss，Inc.
Neuritin I (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/ prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P=0.024 and P=0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rsl475157- rs9405890 haplotypes revealed a highly significant association with the abstraction component of current ("fluid") intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of "fluid" intelligence. (C) 2009 Wiley-Liss, Inc.