1. A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis
- Author
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Rajnish Mehrotra, Ian B. Stanaway, Gail P. Jarvik, Mark Lambie, Johann Morelle, Jeffrey Perl, Jonathan Himmelfarb, Olof Heimburger, David W. Johnson, Talha H. Imam, Bruce Robinson, Peter Stenvinkel, Olivier Devuyst, Simon J. Davies, Ronald Pisoni, David Johnson, Yeoungjee Cho, Muh Geot Wong, Amanda Mather, Bruce Cooper, Eric Goffin, Bert Bammens, Philippe Bovy, Peter Margetts, Paul Taylor, Arsh Jain, Vanita Jassal, Ying Kuan, Camille Harron, Indranil Dasgupta, John Stoves, Habib Akbani, Sumith Abeygunasekara, Edward Sharples, Paul Mead, Amer Hayat, Neal Morgan, Hilary Cramp, Susan Robertson, Richard Fielding, Edwina Brown, Helen Collinson, Pravene Ande, Tim Doulton, Iain MacDougall, Hugh Cairns, Enric Vilar, Anand Vardhan, James Chess, Kanwaljit Sandhu, Martin Wilkie, Gavin McHaffie, Robert Lewis, Lavanya Kamesh, Kate Buck, Robert Peel, Jo Taylor, Paul Johnston, Janson Leung, Coralie Bingham, Hameed Anijeet, Ramzana Asghar, Satish Ranakrishna, Sunita Nair, Neil Iggo, David Lewis, Uday Udayaraj, Susan Dawson, Graham Woordrow, Thangavelu Chandrasekar, Rizwan Hamer, Jonathan Barratt, Richard Baines, Simon Davies, Kieron Donovan, Colin Jones, Christina Ynares, Carl Dukes, Kristin Corapi, Sagar Nigwekar, Osman Khawar, Daniel Weiner, Wei Ling Lau, Kevin Harley, Arshia Ghaffari, Ramesh Saxena, Josephine Abraham, Kerri L. Cavanaugh, Thomas A. Golper, John M. Burkart, James L. Pirkle, Brent Miller, Judy Jang, Jeffrey Turner, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
- Subjects
0301 basic medicine ,Nephrology ,medicine.medical_specialty ,epithelial mesenchymal transition ,medicine.medical_treatment ,030232 urology & nephrology ,Locus (genetics) ,Genome-wide association study ,Peritoneal equilibration test ,Gastroenterology ,Article ,Peritoneal dialysis ,RC902 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Dialysis Solutions ,medicine ,Humans ,genetics ,Renal Insufficiency ,genome wide association study ,Kidney ,business.industry ,Genetic variants ,R735 ,Heritability ,kidney failure ,030104 developmental biology ,medicine.anatomical_structure ,peritoneal dialysis ,Creatinine ,Kidney Failure, Chronic ,peritoneal solute transfer rate ,Peritoneum ,RB ,business ,Peritoneal Dialysis ,Genome-Wide Association Study - Abstract
Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. Heritability of PSTR was estimated using genomic-restricted maximum-likelihood analysis, and the association of PSTR with a genome-wide polygenic risk score was also tested. The mean four-hour dialysate/plasma creatinine ratio in participants was 0.70. In 2212 participants of European ancestry, no signal reached genome-wide significance but 23 single nucleotide variants at four loci demonstrated suggestive associations with PSTR. Meta-analysis of ancestry-stratified regressions in 2850 participants revealed five single-nucleotide variants at four loci with suggestive correlations with PSTR. Association across ancestry strata was consistent for rs28644184 at the KDM2B locus. The estimated heritability of PSTR was 19%, and a permuted model polygenic risk score was significantly associated with PSTR. Thus, this genome-wide association study of patients receiving peritoneal dialysis bolsters evidence for a genetic contribution to inter-individual variability in PSTR.
- Published
- 2021