A genome-wide search for genetic influences and biological pathways related to the brain's white matter integrity
A genome-wide search for genetic influences and biological pathways related to the brain's white matter integrity
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DOI：
10.1016/j.neurobiolaging.2012.02.003
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发表时间：
2012-08-01
影响因子：
4.2
通讯作者：
Deary, Ian J.
中科院分区：
文献类型：
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作者：
Lopez, Lorna M.;Bastin, Mark E.;Deary, Ian J.
1936年Lothian出生队列(LBC1936)对影响老年大脑白质完整性的基因变异进行了全基因组搜索。LBC1936的成员在大约73岁时接受了扩散磁共振成像，用定量纤维束造影术分割了12条白质束，并确定了束平均水扩散参数(n=668)。白质束完整性的全球测量g(FA)来自于束平均分数各向异性测量的主成分分析，它解释了12个白质束个体差异的38.6%。用g(FA)对具有542,050个单核苷酸多态(SNPs)的个体进行全基因组搜索。没有一个单一的SNP关联在全基因组范围内显著(所有p>；5 x 10(-8))。有全基因组的证据提示存在两个SNP，一个位于ADAMTS18(p=1.65 x 10(-6))，与肿瘤抑制和止血有关；另一个位于LOC388630(p=5.08 x 10(-6))，功能未知。尽管在基于单基因的测试中，没有基因通过多重比较的校正，但生物通路分析表明，与g(FA)相关的神经元传递和细胞黏附通路的过度表达。(C)2012 Elsevier Inc.保留所有权利。
A genome-wide search for genetic variants influencing the brain's white matter integrity in old age was conducted in the Lothian Birth Cohort 1936 (LBC1936). At similar to 73 years of age, members of the LBC1936 underwent diffusion MRI, from which 12 white matter tracts were segmented using quantitative tractography, and tract-averaged water diffusion parameters were determined (n = 668). A global measure of white matter tract integrity, g(FA), derived from principal components analysis of tract-averaged fractional anisotropy measurements, accounted for 38.6% of the individual differences across the 12 white matter tracts. A genome-wide search was performed with g(FA) on 535 individuals with 542,050 single nucleotide polymorphisms (SNPs). No single SNP association was genome-wide significant (all p > 5 x 10(-8)). There was genome-wide suggestive evidence for two SNPs, one in ADAMTS18 (p = 1.65 x 10(-6)), which is related to tumor suppression and hemostasis, and another in LOC388630 (p = 5.08 x 10(-6)), which is of unknown function. Although no gene passed correction for multiple comparisons in single gene-based testing, biological pathways analysis suggested evidence for an over-representation of neuronal transmission and cell adhesion pathways relating to g(FA). (C) 2012 Elsevier Inc. All rights reserved.