Genetically Determined Levels of mTOR-Dependent Circulating Proteins and Risk of Multiple Sclerosis

Autor: Yao-Chen Zhang, Ke-Yi Fan, Qi Wang, Jing-Xi Hu, Qian Wang, He-Yi Zhang, Shan Song, Rong Zhao, Jun Qiao, Sheng-Xiao Zhang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Neurology and Therapy, Vol 12, Iss 3, Pp 751-762 (2023)
Druh dokumentu: article
ISSN: 2193-8253
2193-6536
DOI: 10.1007/s40120-023-00455-y
Popis: Abstract Background Results from observational studies indicate an association between circulating levels of mammalian target of rapamycin (mTOR)-dependent circulating proteins and the risk of multiple sclerosis (MS). However, a causal association has not been fully elucidated. Mendelian randomization (MR) is used to overcome limitations inherent to observational studies, assess the causal association, and minimize bias due to confounding and reverse causation. Methods To explore the causal association between seven mTOR-dependent proteins (AKT, RP-S6K, eIF4E-BP, eIF4A, eIF4E, eIF4G, and PKC-α) and MS, we obtained summary statistics from the genome-wide association study (GWAS) meta-analysis of the International Multiple Sclerosis Genetics Consortium (47,429 patients and 68,374 controls) and the INTERVAL study (genetic associations with 2994 plasma proteins from 3301 healthy individuals). MR analyses were conducted using inverse variance weighted, weighted median estimator, and MR-Egger regression methods/models. Sensitivity analyses were performed to ensure the reliability of the findings. Single nucleotide polymorphisms (SNPs) that are independent (r 2
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