Genetics of microstructure of cerebral white matter using diffusion tensor imaging.
Genetics of microstructure of cerebral white matter using diffusion tensor imaging.
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DOI：
10.1016/j.neuroimage.2010.01.078
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发表时间：
2010-11-15
期刊：
影响因子：
5.7
通讯作者：
Blangero, J.
中科院分区：
文献类型：
--
作者：
Kochunov, P.;Glahn, D. C.;Lancaster, J. L.;Winkler, A. M.;Smith, S.;Thompson, P. M.;Almasy, L.;Duggirala, R.;Fox, P. T.;Blangero, J.
我们使用扩散张量成像(DTI)分析了大脑白质(WM)微结构中受试者间变异的遗传控制程度。我们对全脑和10个主要的大脑WM区进行了遗传力、遗传相关和数量性状基因座(QTL)分析。以分数各向异性(FA)、径向(L⊥)和轴向(L||)扩散系数的平均测量值作为数量性状。对467例健康个体(男182例，女285例；平均年龄47.9±13.5岁；年龄范围19-85岁)进行了分析。FA(h2=.52±.11；p=10−7)和L⊥(h2=.37±.14；p=0.001)有显著的遗传力，而L的测量结果没有显著的遗传性(h2=.09±.12；p=.20)。遗传相关分析表明，FA和L⊥的遗传方差贡献率为46%。区域分析揭示了遗传控制的区域差异模式，这与个体发育因素无关，例如区域峰值年龄FA值和FA年龄相关变化率。位于染色体15q25上的标记D15S816上的全脑平均FA(LOD=2.36)和位于染色体3q27上的标记D3S1754附近的L⊥(LOD=2.24)。据报道，这些位点与两种精神障碍(严重抑郁症和强迫症)有显着的共同遗传，在这两种疾病中，患者表现出脑白质的特征性改变。我们的发现表明，大脑白质的微观结构受到强大的基因控制，在健康人群和脑相关疾病患者中进行进一步研究，以确定可能影响大脑白质的基因势在必行。
We analyzed the degree of genetic control over intersubject variability in the microstructure of cerebral white matter (WM) using diffusion tensor imaging (DTI). We performed heritability, genetic correlation and quantitative trait loci (QTL) analyses for the whole-brain and 10 major cerebral WM tracts. Average measurements for fractional anisotropy (FA), radial (L⊥) and axial (L||) diffusivities served as quantitative traits. These analyses were done in 467 healthy individuals (182 males/285 females; average age 47.9±13.5 years; age range:19–85 years), recruited from randomly-ascertained pedigrees of extended families. Significant heritability was observed for FA (h2=.52±.11;p=10−7) and L⊥(h2=.37±.14; p=0.001), while L|| measurements were not significantly heritable (h2=.09±.12; p=.20). Genetic correlation analysis indicated that the FA and L⊥ shared 46% of the genetic variance. Tract-wise analysis revealed a regionally diverse pattern of genetic control, which was unrelated to ontogenic factors, such as tract-wise age-of-peak FA values and rates of age-related change in FA. QTL analysis indicated linkages for whole-brain average FA (LOD=2.36) at the marker D15S816on chromosome 15q25, and for L⊥(LOD=2.24) near the marker D3S1754 on the chromosome 3q27. These sites have been reported to have significant co-inheritance with two psychiatric disorders (major depression and obsessive-compulsive disorder) in which patients show characteristic alterations in cerebral WM. Our findings suggest that the microstructure of cerebral white matter is under a strong genetic control and further studies in healthy as well as patients with brain-related illnesses are imperative to identify the genes that may influence cerebral white matter.
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DOI：
10.1073/pnas.0402680101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Gogtay, N;Giedd, JN;Thompson, PM
通讯作者：
Thompson, PM
影响因子：
7.1
作者：
Choquette, Anne C.;Lemieux, Simone;Perusse, Louis
通讯作者：
Perusse, Louis
影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
影响因子：
3.1
作者：
CHEVERUD, JM;FALK, D;HILDEBOLT, C
通讯作者：
HILDEBOLT, C
影响因子：
5.3
作者：
Hoeft, Fumiko;Barnea-Goraly, Naama;Reiss, Allan L.
通讯作者：
Reiss, Allan L.