全蛋白质组孟德尔随机化分析探索不宁腿综合征的药物治疗靶点

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【中图分类号】R741 【文献标识码】A

ldentification of potential drug targets for restless legs syndrome by Mendelian randomizationanalysis based on plasma proteomics

ZHANG Qinli1， XU Hua²， HAN Xiuyan²， LIU Hong1

1.DepartmentofNeurology，Heping Hospital Afliated to Changzhi Medical College，Changzhi 046000，

Shanxi Province， China

2.The First Clinical College， Changzhi Medical Collge， Changzhi O46ooo，Shanxi Province， China

Corresponding author： LIU Hong， Email： hpsjbxjys@163.com

【Abstract】 Objective To evaluate the causal relationship between plasma proteins and restless legs syndrome （RLS） by proteome-wide Mendelian randomization （MR） and to explore new therapeutic targets for RLS. Methods Genome-wide association studies （GWAS） data of plasma proteins were obtained from the UK Biobank，and GWAS data of RLS were extracted from the FinnGen R11 database. Colocalization analysis was performed to identify the common causal variants between plasma proteins and RLS. Results MR analysis showed that plasma proteins ASPSCR1[OE λ=0.678 0 95%CI （0.544，0.847）]and C1QTNF5 [OI λ=0.526 ， 95%CI （0.367，0.752）] had aprotective effecton RLS;plasma proteinsKRT19[OR .=1.769 95%CI （1.283，2.439）] and LAT2 [OR ， 95%CI （2.206，13.893）] were associated with the increased risk of RLS. Colocalization analysis showed that among the 4 plasma proteins，LAT2 had a strong causal variation relationship， while ASPSCR1， C1QTNF5，and KRT19 had a moderate causal variation relationship.The protein functional network suggested that protein-associated genes related to RLS were significantly enriched in sugar transmembrane transporter activity，carbohydrate transmembrane transportactivity，and Fc receptor signaling pathway. Conclusion This study identifies the causal relationship between 4 plasma proteins and RLS，which provides potential therapeutic targets for the treatment of RLS，but further studies are needed to confirm it.

【Keywords】Restless legs syndrome; Mendelian randomization; Drug targets; Plasma proteomics

不宁腿综合征（restlesslegs syndrome，RLS）是一种常见的主要累及腿部的中枢性感觉运动障碍性疾病，其典型临床表现为睡眠期间或睡前双下肢有不舒服的感觉及强烈移动腿的冲动，因此被归类为睡眠相关运动障碍[]。（剩余14635字）