Published December 10, 2018
| Version v1
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Data from: Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
Authors/Creators
- Xu, Xiaoguang1
- Eales, James M.1
- Akbarov, Artur1
- Guo, Hui1
- Becker, Lorenz1
- Talavera, David1
- Ashraf, Fezhan1
- Nawaz, Jabran1
- Pramanik, Sanjeev1
- Bowes, John1
- Jiang, Xiao1
- Dormer, John2
- Denniff, Matthew3
- Antczak, Andrzej4
- Szulinska, Monika5
- Wise, Ingrid6
- Prestes, Priscilla R.6
- Glyda, Maciej7
- Bogdanski, Pawel8
- Zukowska-Szczechowska, Ewa9
- Berzuini, Carlo1
- Woolf, Adrian S.10
- Samani, Nilesh J.3
- Charchar, Fadi J.3
- Tomaszewski, Maciej1
- 1. University of Manchester
- 2. University Hospitals of Leicester NHS Trust
- 3. University of Leicester
- 4. Department of Urology and Uro-oncology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland*
- 5. Department of Internal Medicine, Metabolic Disorders and Hypertension, Karol Marcinkowski University of Medical Sciences, Poznan, Poland*
- 6. Federation University
- 7. University of Zielona Góra
- 8. Department of Obesity and Metabolic Disorders Treatment and Clinical Dietetics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland*
- 9. Department of Health Care, Silesian Medical College, Katowice, Poland*
- 10. Manchester University NHS Foundation Trust
Description
Genome-wide association studies (GWAS) have identified >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.
Notes
Files
TRANSLATE-genes.txt
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Additional details
Related works
- Is cited by
- 10.1038/s41467-018-07260-4 (DOI)