{
  "abstract": "Background and hypothesis Chronic kidney disease (CKD) is a global health and economic burden, particularly among individuals with type 2 diabetes (T2D). According to Kidney Disease: Improving Global Outcomes guidelines, key CKD indicators include urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Although independent genetic loci for these traits have been reported, their shared genetic architecture remains insufficiently understood. We hypothesized that there are shared genetic markers of kidney function (eGFR) and albuminuria generally, but also specific to the T2D population.Methods We conducted a cross-sectional observational study including 432 451 UK Biobank participants of primarily European descent (94%), with a subgroup of 16 265 with T2D after data quality control. We examined whether 423 single-nucleotide polymorphisms previously associated with eGFR in a large genome-wide association study meta-analysis were associated with (a) eGFR estimated using the 2021 race-free CKD-Epidemiology Collaboration creatinine equation (eGFR 2021) and (b) UACR. Multiple linear regression models were adjusted for systolic blood pressure, age, sex, and the first 10 genetic principal components to account for population stratification. Analyses were performed using Python and R. Bonferroni correction (BC) was performed. For the T2D subgroup, the models were additionally adjusted for body mass index and glycated hemoglobin.Results In the overall population, 422 loci were nominally associated with eGFR 2021, of which 75 were nominally associated with UACR (p≤0.05); 12 remained significant after BC (Pb ≤ 1.18×10-4). In the T2D subgroup, 76 loci nominally associated with eGFR2021, six also associated nominally with UACR (p≤0.05), and one remained significant after BC (Pb ≤ 6.58×10-4). Two pleiotropic loci (GSTA2, USP2-AS1) suggested diabetes-specific effects.Conclusion This study identifies several shared genetic loci underlying eGFR and UACR in both general and T2D European populations. These findings highlight common pathobiological pathways between albuminuria and reduced kidney function and provide a genetic map that may inform future CKD risk stratification and towards the development of therapeutic targets.",
  "authors": [
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark"
      ],
      "name": "Cilia Naaman"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark"
      ],
      "name": "Frederik Persson"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Thomas Kümler"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark"
      ],
      "name": "Simone Theilade"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark",
        "Departments of Medicine, Epidemiology and Population Health, and Health Policy, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Glenn Chertow"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Peter Rossing"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Tine Hansen"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Denmark",
        "The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark",
        "Department of Science and Environment, Roskilde University, Roskilde, Denmark"
      ],
      "name": "Tarunveer S Ahluwalia"
    }
  ],
  "title": "Mapping shared genetic determinants of eGFR and albuminuria with a focus on type 2 diabetes: a large-scale European study",
  "uid": "5afd10a3-a421-51c9-8d07-57a8d2def26c"
}