RT期刊文章SR电子T1评估代理神经发育语言表型和基因之间的关联的风险原发性进行性失语摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯10.1212 SP / WNL。半岛投注体育官网0000000000207136 10.1212 / WNL。0000000000207136 A1 Nassan,马利克A1水虎鱼,新年代A1 Rogalski,艾米丽A1 Geula, Changiz A1 Mesulam, M-Marsel A1 eric reiman,马特年2023 UL //www.ebmtp.com/content/ea半岛投注体育官网rly/2023/03/08/WNL.0000000000207136.abstract AB背景和目的:原发性进行性失语(PPA)是一种神经退行性综合征进步语言的衰落。PPA有3个主要的亚型:logopenic,语义,agrammatic。观察性研究表明语言之间的关联相关的神经发育表型和PPA的风险增加。我们试图评估这种关系通过孟德尔随机化(MR)的方法,它可以显示潜在的因果关联。方法:全基因组重要的单核苷酸多态性(snp)与阅读障碍(42个snp)联系在一起,发展语言障碍(SNPs) 29日和左撇子(41个snp),被用作基因风险代理。18/41单核苷酸多态性的左撇子与大脑皮层的结构不对称有关。GWAS摘要统计信息来源于公开数据库语义(308例/ 616控制)和agrammatic PPA(269例/ 538控制)。logopenic PPA(324例/ 3444控制)被代理通过近似的标题与突出语言障碍的临床诊断阿尔茨海默氏症”。倒数加权方差进行先生为主要分析测试风险和结果之间的关系。 Sensitivity analyses were completed to test the robustness of the results.Results: Dyslexia, developmental speech disorders and left-handedness were not associated with any PPA subtype (P > 0.05). The genetic proxy of cortical asymmetry in left handedness was significantly associated with agrammatic PPA (beta = 4.3, P= 0.007), but not with other PPA subtypes. This association was driven by microtubule-related genes, primarily by a variant that is in complete linkage disequilibrium with MAPT gene. Sensitivity analyses were overall consistent with the primary analyses.Discussion: Our results do not support a causal association between dyslexia, developmental speech disorders, or handedness with any of the PPA subtypes. Our data suggests a complex association between cortical asymmetry genes and agrammatic PPA. Whether the additional association with left handedness is necessary remains to be determined but is unlikely given the absence of association between left handedness and PPA. Genetic proxy of brain asymmetry (regardless of handedness) was not tested as an exposure due to lack of suitable genetic proxy. Furthermore, the genes related to cortical asymmetry associated with agrammatic PPA are implicated in microtubule-related proteins (TUBA1B, TUBB, and MAPT), which is keeping with the association of tau-related neurodegeneration in this PPA variant.