Incorporating local ancestry information to predict genetically associated DNA methylation in admixed populations
Methylome-wide association studies (MWASs) have identified many 5'-cytosine-phosphate-guanine-3' (CpG) sites associated with complex traits. Several methods have been developed to predict CpG methylation levels from genotypes when the direct measurements of methylation are unavailable. To date, the published methods have mostly used datasets from populations of European ancestry to train prediction models for methylations, which limits the generalizability of methylome-wide association study to non-European populations. To address this gap, we proposed a new model by incorporating local ancestry (LA) information, called LA Methylation Predictor with Preselection (LAMPP), to improve the prediction accuracy of DNA methylation in admixed populations. We showed that LAMPP outperformed the conventional model and other LA models in prediction accuracy using an admixed African American population. We further applied our model to identify significant CpG sites for seven complex traits. Together, our LAMPP model is a valuable tool to reveal epigenetic underpinnings of complex traits in the admixed populations.
Authors
- Bradley E. Aouizerat (ORCID: https://orcid.org/0000-0002-6047-9397)
- Youshu Cheng (ORCID: https://orcid.org/0009-0006-6398-2082)
- Amy C. Justice (ORCID: https://orcid.org/0000-0003-0139-5502)
- Claudia Martinez (ORCID: https://orcid.org/0000-0002-2489-6193)
- Geyu Zhou (ORCID: https://orcid.org/0000-0002-4049-0193)
- Ke Xu (ORCID: https://orcid.org/0000-0002-6472-7052)
- Hongyu Zhao (ORCID: https://orcid.org/0000-0003-1195-9607)
- Xinyu Zhang (ORCID: https://orcid.org/0000-0001-7077-3314)
- Hongyu Li (ORCID: https://orcid.org/0000-0001-6525-9310)
Institutions
- University of Miami (US)
- Yale University (US)
- VA Connecticut Healthcare System (US)
- Yale New Haven Health System (US)
- Center for Clinical Research (United States) (US)
- New York University (US)
- New York College of Health Professions (US)
Publication Details
- Journal
- Briefings in Bioinformatics
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1093/bib/bbaf325
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- U.S. Department of Veterans Affairs
- Yale University
- Northwestern University
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- University of California, San Francisco
- Center for AIDS Research, University of Alabama at Birmingham
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute on Deafness and Other Communication Disorders
- National Institute of Nursing Research
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research
- National Institute on Minority Health and Health Disparities
- Center for AIDS Research, University of North Carolina at Chapel Hill
- Clinical and Translational Science Institute, University of California, Los Angeles