Predicting White Matter Integrity from Multiple Common Genetic Variants
Predicting White Matter Integrity from Multiple Common Genetic Variants
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DOI：
10.1038/npp.2012.49
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发表时间：
2012-08-01
影响因子：
7.6
通讯作者：
Thompson, Paul M.
中科院分区：
文献类型：
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作者：
Kohannim, Omid;Jahanshad, Neda;Thompson, Paul M.
最近发现几种常见的遗传变异似乎影响白色物质的微观结构，如通过扩散张量成像（DTI）测量的。每一种遗传变异只能解释大脑微观结构变异的一小部分，因此我们着手探索它们对胼胝体白色物质完整性的综合影响。我们测量了COMT、NTRK 1、BDNF、ErbB 4、CLU和HFE基因中的6个常见候选单核苷酸多态性（SNP），并研究了它们对395名健康成年双胞胎和同胞（年龄：20-30岁）的白色结构的个体和聚集效应。所有受试者均接受4-T 94方向高角分辨率弥散成像扫描。当使用混合效应线性回归组合时，基于五个候选SNP（COMT，NTRK 1，ErbB 4，CLU和HFE）的联合模型解释了胼胝体平均各向异性分数（FA）的6%的方差。该预测模型对82%的胼胝体素（包括胼胝体、体部和压部）的FA具有可检测的影响。从基因型预测大脑的纤维微观结构可能最终有助于早期风险评估，并最终有助于对影响大脑完整性和连通性的神经精神疾病进行个性化治疗。Neuropsychopharmacology（2012）37，2012-2019; doi：10.1038/npp.2012.49; 2012年4月18日在线发表
Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20-30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained similar to 6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected. Neuropsychopharmacology (2012) 37, 2012-2019; doi:10.1038/npp.2012.49; published online 18 April 2012