{
  "abstract": "Background Implementing lipid control in patients with diabetes is regarded as a potential strategy for halting the advancement of diabetic retinopathy (DR). This study seeks to use Mendelian randomisation (MR) to assess the causal relationship between lipid traits and lipid-lowering drug targets and full-course DR (background DR, severe non-proliferative DR (NPDR) and proliferative DR (PDR)).Methods A two-sample MR and drug target MR to decipher the causal effects of lipid traits and lipid-lowering drug targets on full-course DR, including background DR, severe NPDR and PDR, was conducted in the study. Genetic variants associated with lipid traits and genes encoding the protein targets of lipid-lowering drugs were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data of full-course DR are obtained from FinnGen.Results No significant causal relationship was found between lipid traits and full-course DR. However, in drug target MR analysis, peroxisome proliferator-activated receptor gamma (PPARG) enhancement was associated with lower risks of background DR (OR=0.12, p=0.005) and PDR (OR=0.25, p=0.006). Additionally, mediation MR analysis showed that lowering fasting insulin (p=0.015) and HbA1c (p=0.005) levels mediated most of the association between PPARG and full-course DR.Conclusions This study reveals PPARG may be a promising drug target for full-course DR. The activation of PPARG could reduce the risk of full-course DR, especially background DR and PDR. The mechanism of the PPARG agonists’ protection of full-course DR may be dependent on the glucose-lowering effect.",
  "authors": [
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Jiahui Cao"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Ting Su"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Shuilian Chen"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Zijing Du"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Chunran Lai"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Kaiyi Chi"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Qinyi Li"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Shan Wang"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Qiaowei Wu"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yunyan Hu"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Ying Fang"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yijun Hu"
    },
    {
      "affiliations": [
        "Royal Victorian Eye and Ear Hospital, Centre for Eye Research Australia Ltd, East Melbourne, Victoria, Australia"
      ],
      "name": "Zhuoting Zhu"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Yu Huang"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiayin Zhang"
    },
    {
      "affiliations": [
        "Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Honghua Yu"
    }
  ],
  "title": "Evaluating lipid-lowering drug targets for full-course diabetic retinopathy",
  "uid": "aa57774d-d4e8-5f59-988e-ace420327db2"
}