Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, The Netherlands.
Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Mar;4(3):243-250. doi: 10.1016/j.bpsc.2018.07.010. Epub 2018 Aug 3.
Genome-wide association studies have identified numerous genetic variants that predispose to neuropsychiatric traits. Identification of mechanisms in the brain that underlie these associations is essential for understanding manifestations of genetic predisposition within the general population. Here, we investigated the association between polygenic scores (PGSs) for seven neuropsychiatric traits and white matter microstructure of the brain on diffusion tensor imaging in the pediatric population.
Participants from the Generation R Study who had genotype and diffusion tensor imaging data available (n = 1138, mean age = 10.2 years, range = 8.7-12.0) were included. PGSs were calculated for five psychiatric disorders (attention-deficit/hyperactivity disorder, bipolar disorder, autism, major depressive disorder, and schizophrenia) and two cognitive traits (intelligence and educational attainment) and were tested for associations with global and tract-specific fractional anisotropy (FA) and mean diffusivity.
Significant positive associations with global FA were observed for the PGSs of intelligence (β = .109, SE = .029, p < .001, ΔR = .012) and educational attainment (β = .118, SE = .029, p < .001, ΔR = .014). No significant associations were observed with FA for the PGSs of psychiatric disorders. Tract-specific analysis showed that the PGSs for intelligence and educational attainment were associated with FA of several association and projection fibers of the brain.
Our results show that genetic predisposition for cognition-related traits, but not for psychiatric disorders, is associated with microstructural diffusion measures of white matter tracts at an early age. These results suggest a shared genetic etiology among structural connectivity, intelligence, and educational achievement.
全基因组关联研究已经确定了许多使神经精神特征易于发生的遗传变异。确定大脑中这些关联的机制对于理解一般人群中遗传易感性的表现至关重要。在这里，我们研究了七种神经精神特征的多基因评分（PGS）与儿科人群弥散张量成像中的脑白质微观结构之间的关联。
纳入了具有基因型和弥散张量成像数据的 Generation R 研究参与者（n=1138，平均年龄为 10.2 岁，范围为 8.7-12.0）。为五种精神障碍（注意缺陷/多动障碍、双相障碍、自闭症、重度抑郁症和精神分裂症）和两种认知特征（智力和受教育程度）计算了 PGS，并测试了它们与全脑和束特异性分数各向异性（FA）和平均扩散系数的相关性。
智力和教育程度 PGS 与全脑 FA 呈显著正相关（β=0.109，SE=0.029，p<0.001，ΔR=0.012；β=0.118，SE=0.029，p<0.001，ΔR=0.014）。精神障碍 PGS 与 FA 无显著相关性。束特异性分析表明，智力和教育程度 PGS 与大脑的几个联合和投射纤维的 FA 相关。
我们的结果表明，与认知相关特征相关的遗传易感性，但与精神障碍无关，与白质束的微观扩散测量值在早期就有关联。这些结果表明，结构连接、智力和教育成就之间存在共同的遗传病因。
