TY - JOUR AB - BACKGROUND: Polygenic scores (PGSs) combining genetic variants found to be associated with creatinine-based estimated glomerular filtration rate (eGFRcrea) have been applied in various study populations with different age ranges. This has shown that PGS explain less eGFRcrea variance in the elderly. Our aim was to understand how differences in eGFR variance and the percentage explained by PGS varies between population of general adults and elderly. RESULTS: We derived a PGS for cystatin-based eGFR (eGFRcys) from published genome-wide association studies. We used the 634 variants known for eGFRcrea and the 204 variants identified for eGFRcys to calculate the PGS in two comparable studies capturing a general adult and an elderly population, KORA S4 (n = 2,900; age 24-69 years) and AugUR (n = 2,272, age ≥ 70 years). To identify potential factors determining age-dependent differences on the PGS-explained variance, we evaluated the PGS variance, the eGFR variance, and the beta estimates of PGS association on eGFR. Specifically, we compared frequencies of eGFR-lowering alleles between general adult and elderly individuals and analyzed the influence of comorbidities and medication intake. The PGS for eGFRcrea explained almost twice as much (R2 = 9.6%) of age-/sex adjusted eGFR variance in the general adults compared to the elderly (4.6%). This difference was less pronounced for the PGS for eGFRcys (4.7% or 3.6%, respectively). The beta-estimate of the PGS on eGFRcrea was higher in the general adults compared to the elderly, but similar for the PGS on eGFRcys. The eGFR variance in the elderly was reduced by accounting for comorbidities and medication intake, but this did not explain the difference in R2-values. Allele frequencies between general adult and elderly individuals showed no significant differences except for one variant near APOE (rs429358). We found no enrichment of eGFR-protective alleles in the elderly compared to general adults. CONCLUSIONS: We concluded that the difference in explained variance by PGS was due to the higher age- and sex-adjusted eGFR variance in the elderly and, for eGFRcrea, also by a lower PGS association beta-estimate. Our results provide little evidence for survival or selection bias. AU - Herold, J.M.* AU - Nano, J. AU - Gorski, M.* AU - Winkler, T.W.* AU - Stanzick, K.J.* AU - Zimmermann, M.E.* AU - Brandl, C.* AU - Peters, A. AU - Koenig, W.* AU - Burkhardt, R.* AU - Gessner, A.* AU - Heid, I.* AU - Gieger, C. AU - Stark, K.J.* C1 - 67889 C2 - 54367 CY - Campus, 4 Crinan St, London N1 9xw, England TI - Polygenic scores for estimated glomerular filtration rate in a population of general adults and elderly - comparative results from the KORA and AugUR study. JO - BMC Genom Data VL - 24 IS - 1 PB - Bmc PY - 2023 SN - 2730-6844 ER - TY - JOUR AB - BACKGROUND: MicroRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. RESULTS: A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. CONCLUSIONS: miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies. AU - van der Vorst, E.P.C.* AU - Pepe, M. AU - Peters, L.J.F.* AU - Haberbosch, M.* AU - Jansen, Y.* AU - Nauman, R.* AU - Stathopoulos, G.T. AU - Weber, C.* AU - Bidzhekov, K.* C1 - 62446 C2 - 50877 CY - Campus, 4 Crinan St, London N1 9xw, England TI - Transcriptome signature of miRNA-26b KO mouse model suggests novel targets. JO - BMC Genom Data VL - 22 IS - 1 PB - Bmc PY - 2021 SN - 2730-6844 ER - TY - JOUR AB - Following publication of the original article [1], the authors identified an error in the author name of Ronald Naumann. The incorrect author name is: Ronald Nauman The correct author name is: Ronald Naumann The author group has been updated above and the original article [1] has been corrected. AU - van der Vorst, E.P.C.* AU - Pepe, M. AU - Peters, L.J.F.* AU - Haberbosch, M.* AU - Jansen, Y.* AU - Naumann, R.* AU - Stathopoulos, G.T. AU - Weber, C.* AU - Bidzhekov, K.* C1 - 63031 C2 - 51219 CY - Campus, 4 Crinan St, London N1 9xw, England TI - Correction to: Transcriptome signature of miRNA-26b KO mouse model suggests novel targets. JO - BMC Genom Data VL - 22 IS - 1 PB - Bmc PY - 2021 SN - 2730-6844 ER -