PDF(Pubmed)
Abstract：
Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain.
摘要：
先前对自闭症谱系障碍（ASD）的研究表明小脑和脑干的重要体积改变。然而，大多数这些研究仅限于临床样本较小的病例对照研究，主要包括儿童或青少年。在这里，我们旨在探索累积遗传负荷(多基因风险评分，PRS）用于ASD和小脑和脑干的体积改变，以及人口水平的成年人大脑的整体脑组织体积。我们利用了精神病学遗传学协会对ASD的最新全基因组关联研究(18,381例，27,969个对照)，并在一个独立的队列中构建了ASDPRS，英国生物银行进行了回归分析，以进行多重比较，错误发现率（FDR）为5％，以调查约31,000名参与者中ASDPRS与44种脑磁共振成像（MRI）表型之间的关联。主要分析包括16种MRI表型：大脑总体积，脑脊液（CSF），灰质(GM)，白质（WM），整个小脑的GM，脑干,和小脑的十个区域(I_IV，V,VI,VIIb,VIIIa,VIIIb,IX,X,克鲁斯和克鲁斯二世）。次要分析包括28种MRI表型：小脑的亚区域体积，包括Vermis的GM以及每个小脑区域的左右小叶。ASDPRS与七个大脑区域的体积显着相关，较高的PRS与整个大脑的体积减少有关，WM,脑干,和小脑I-IV区，IX,X,和CSF的体积增加。三个次区域体积，包括左小脑小叶I-IV，小脑vermesVIIIb，和X与ASDPRS呈显著负相关。这项研究强调了ASD易感性之间的实质性联系，其潜在的遗传病因，和成人大脑的神经解剖学改变。
