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Meta-Analysis

Identification of RNA modification-associated single-nucleotide polymorphisms in genomic loci for low-density lipoprotein cholesterol concentrations

    Fan Tang‡

    Department of Epidemiology, Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, China

    ‡These authors contributed equally to this work

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    ,
    Chengcheng Duan‡

    Department of Epidemiology, Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, China

    ‡These authors contributed equally to this work

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    ,
    Ru Li

    Department of Epidemiology, Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, China

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    ,
    Huan Zhang

    **Author for correspondence: Tel.: +86 512 6588 3227;

    E-mail Address: hzhang3@suda.edu.cn

    Department of Epidemiology, Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, China

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    &
    Xingbo Mo

    *Author for correspondence:

    E-mail Address: xbmo@suda.edu.cn

    Department of Epidemiology, Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, China

    Center for Genetic Epidemiology & Genomics, School of Public Health, Medical College of Soochow University, China

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    Published Online:26 Jul 2022https://doi.org/10.2217/pgs-2022-0041

    Abstract

    Introduction: Genome-wide association studies have identified approximately 1000 lipid-associated loci, but functional variants are less known. Materials & methods: The authors identified RNA modification-related single-nucleotide polymorphisms (RNAm-SNPs) in summary data from a genome-wide association study. By applying Mendelian randomization analysis, the authors identified gene expression levels involved in the regulation of RNAm-SNPs on low-density lipoprotein cholesterol (LDL-C) levels. Results: The authors identified 391 RNAm-SNPs that were significantly associated with LDL-C levels. RNAm-SNPs in NPC1L1, LDLR, APOB, MYLIP, LDLRAP1 and ABCA6 were identified. The RNAm-SNPs were associated with gene expression. The expression levels of 112 genes were associated with LDL-C levels, and some of them (e.g., APOB, SMARCA4 and SH2B3) were associated with coronary artery disease. Conclusion: This study identified many RNAm-SNPs in LDL-C loci and elucidated the relationship among the SNPs, gene expression and LDL-C.

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