PDF(Pubmed)
Abstract：
Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer\'s disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.
摘要：
先前的观察研究表明，结构和扩散成像衍生的表型（IDPs）与主要的神经退行性疾病相关；然而，这些关联是否是因果关系在很大程度上仍不确定.在这里，我们进行了双向双样本孟德尔随机化分析，以使用常见的遗传变异-单核苷酸多态性（SNP）作为工具变量来推断结构和扩散IDPs与主要神经退行性疾病之间的因果关系。从英国生物库队列中的33,224名个体获得了结构和扩散IDPs的全基因组关联研究（GWAS）的摘要统计。七种主要神经退行性疾病的GWAS的汇总统计是从迄今为止每种疾病的最大GWAS获得的。正向MR分析确定了遗传预测的三种结构性IDP对阿尔茨海默病（AD）的显着或暗示性统计因果影响，额颞叶痴呆(FTD),和多发性硬化症。例如,左侧颞上回表面积的减少与AD的高风险相关.反向MR分析确定了遗传预测的AD的显着或暗示性统计因果效应，路易体痴呆（LBD），和FTD对九个结构和扩散国内流离失所者的影响。例如,LBD与右上纵束平均扩散率增加有关，AD与右腹侧纹状体灰质体积减少有关。我们的发现可能有助于在神经影像学水平上揭示主要神经退行性疾病的预测和治疗干预。
