http://researchonline.federation.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics http://researchonline.federation.edu.au/vital/access/manager/Repository/vital:13808 Wed 07 Apr 2021 14:01:55 AEST ]]> Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies http://researchonline.federation.edu.au/vital/access/manager/Repository/vital:13698 Wed 07 Apr 2021 14:01:48 AEST ]]> Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals http://researchonline.federation.edu.au/vital/access/manager/Repository/vital:14938 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.]]> Thu 25 Nov 2021 11:48:02 AEDT ]]> Molecular insights into genome-wide association studies of chronic kidney disease-defining traits http://researchonline.federation.edu.au/vital/access/manager/Repository/vital:13555 100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.]]> Thu 19 May 2022 11:08:51 AEST ]]> The y chromosome : A blueprint for men's health? http://researchonline.federation.edu.au/vital/access/manager/Repository/vital:13014 Thu 07 Oct 2021 16:13:10 AEDT ]]>