Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study
Background: Neurological disorders, such as Alzheimer's disease (AD), comprise a major cause of health-related disabilities in human. However, biomarkers towards pathogenesis or novel targets are still limited. Objective: To identify the causality between plasma proteins and the risk of AD and other eight common neurological diseases using a Mendelian randomization (MR) study. Methods: Exposure data were obtained from a genome-wide association study (GWAS) of 2,994 plasma proteins in 3,301 healthy adults, and outcome datasets included GWAS summary statistics of nine neurological disorders. Inverse variance-weighted MR method as the primary analysis was used to estimate causal effects. Results: Higher genetically proxied plasma myeloid cell surface antigen CD33 level was found to be associated with increased risk of AD (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.047-1.112, p = 8.39x10(-7)). We also discovered the causality between genetically proxied elevated prolactin and higher risk of epilepsy (OR = 1.068, 95% CI = 1.034-1.102; p = 5.46x10(-5)). Negative associations were identified between cyclin-dependent kinase 8 and ischemic stroke (OR = 0.927, 95% CI = 0.896-0.959, p = 9.32x10(-6)), between neuralized E3 ubiquitin-protein ligase 1 and migraine (OR = 0.914, 95% CI = 0.878-0.952, p = 1.48x10(-5)), and between Fc receptor-like protein 4 and multiple sclerosis (MS) (OR = 0.929, 95% CI = 0.897-0.963, p = 4.27x10(-5)). Conclusion: The findings identified MR-level protein-disease associations for AD, epilepsy, ischemic stroke, migraine, and MS.
基金:
National Natural Science Foundation of China [82220108009, 81970996]; National Key R&D Program of China [2022YFC3602600]; STI2030-Major Projects [2021ZD0201801]; Science and Technology Project of Guangdong Province [2019B030316001]; Guangzhou Municipal Key Discipline in Medicine [2021-2023]
第一作者机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol & Innovat Ctr Neurol Disorders, Natl Ctr Neurol Disorders, Beijing, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol & Innovat Ctr Neurol Disorders, Natl Ctr Neurol Disorders, Beijing, Peoples R China[5]Minist Educ Peoples Republ China, Neurodegenerat Lab, Beijing, Peoples R China[*1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China[*2]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, 45 Changchun St, Beijing 100053, Peoples R China
推荐引用方式(GB/T 7714):
Wei Tao,Shi Xiaolei,Sun Wei,et al.Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study[J].JOURNAL OF ALZHEIMERS DISEASE REPORTS.2023,7(1):811-822.doi:10.3233/ADR-230058.
APA:
Wei, Tao,Shi, Xiaolei,Sun, Wei,Song, Weiyi,Zhou, Shaojiong...&Tang, Yi.(2023).Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study.JOURNAL OF ALZHEIMERS DISEASE REPORTS,7,(1)
MLA:
Wei, Tao,et al."Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study".JOURNAL OF ALZHEIMERS DISEASE REPORTS 7..1(2023):811-822