Abstract: FR-PO917
Quantification of DNA-Methylation at Loci Associated With Metals, Pesticides, and Temperature Provide No Evidence for a Role of These Exposures in the Aetiology of Mesoamerican Nephropathy
Session Information
- CKD: Epidemiology, Risk Factors, Prevention - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention
Authors
- Oomatia, Amin, University College London Department of Renal Medicine, London, London, United Kingdom
- Al-Rashed, Ali M., University College London Department of Renal Medicine, London, London, United Kingdom
- Gonzalez, Marvin Antonio, Research Centre on Health, Work and Environment at National Autonomous University of Nicaragua, Leon, Nicaragua
- Cardenas, Andres, School of Public Health, University of Berkeley, Berkley, California, United States
- Pearce, Neil, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, United Kingdom
- Ecker, Simone, University College London Cancer Institute, London, United Kingdom
- Beck, Stephan, University College London Cancer Institute, London, United Kingdom
- Heggeseth, Brianna, Macalester College, Saint Paul, Minnesota, United States
- Chervova, Olga, University College London Cancer Institute, London, United Kingdom
- Caplin, Ben, University College London Department of Renal Medicine, London, London, United Kingdom
Group or Team Name
- The Colt/UK MRC CKDu study group
Background
Mesoamerican nephropathy (MeN) is a leading cause of death amongst working age men in Central America, yet its aetiology remains unclear. Several potential environmental causes have been proposed including heat-stress, pesticides and heavy metals, but intermittent and cumulative exposures are difficult to capture using biomonitoring. Epigenetic studies have identified DNA-methylation (DNAm) at specific loci associated with these exposures. Therefore, we first conducted an epigenome-wide association study (EWAS) focusing on incident cases. Then, using a hypothesis driven approach, explored the association between DNAm at loci previously associated with implicated exposures and MeN.
Methods
MeN cases from a population-based longitudinal study were empirically derived using a hidden Markov model based on departure from a healthy population eGFR distribution. Our data consisted of 2-3 blood samples collected across a 5-year period from each of 57 incident-cases (pre- and post-evidence of disease onset), 57 matched-controls and 16 established cases. DNAm was quantified (Illumina MethylationEPIC BeadChip) in a total of 320 blood-samples. Raw data were processed using established pipelines. Associations between differentially methylated positions (DMPs) and MeN were examined using covariate-adjusted mixed-effect models, allowing for repeat measures. DMPs previously reported to associate with ambient temperature, arsenic, cadmium, chromium and pesticides, were collated from a systematic search, and potential association of MeN with these loci was investigated.
Results
The EWAS demonstrated no DMPs associated with MeN at standard epigenome-wide statistical thresholds. Furthermore, hypothesis driven analyses examining the coefficients of DMPs reported to be associated with ambient temperature, pesticides and metals, demonstrated no associations with MeN. Further calculations suggested adequate power to detect biologically important differences.
Conclusion
DNAm studies in our dataset do not support the hypotheses that pesticides, temperature or the examined metals have a causal role in early-stage MeN. Therefore, other aetiological factors should be considered.
Funding
- Private Foundation Support