Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

Joshua M. Galanter*, Christopher R. Gignoux, Sam S. Oh, Dara Torgerson, Maria Pino-Yanes, Neeta Thakur, Celeste Eng, Donglei Hu, Scott Huntsman, Harold J. Farber, Pedro C. Avila, Emerita Brigino-Buenaventura, Michael A. Lenoir, Kelly Meade, Denise Serebrisky, William Rodríguez-Cintrón, Rajesh Kumar, Jose R. Rodríguez-Santana, Max A. Seibold, Luisa N. BorrellEsteban G. Burchard, Noah Zaitlen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation.

Original languageEnglish (US)
Article numbere20532
JournaleLife
Volume6
DOIs
StatePublished - Jan 3 2017

Funding

The authors acknowledge the families and patients for their participation and thank the numerous health care providers and community clinics for their support and participation in GALA II. In particular, the authors thank study coordinator Sandra Salazar; the recruiters who obtained the data: Duanny Alva, MD, Gaby Ayala-Rodriguez, Lisa Caine, Elizabeth Castellanos, Jaime Colon, Denise DeJesus, Blanca Lopez, Brenda Lopez, MD, Louis Martos, Vivian Medina, Juana Olivo, Mario Peralta, Esther Pomares, MD, Jihan Quraishi, Johanna Rodriguez, Shahdad Saeedi, Dean Soto, Ana Taveras. We also thank Sasha Gusev for helpful discussion. Computations in this manuscript were performed using the UCSF Biostatistics High Performance Computing System. National Institutes of Health. American Asthma Foundation. Sandler Family Foundation. Tobacco-Related Disease Research Program, 24RT-0025. Flight Attendant Medical Research Institute. Hewett Fellowship. Parker B. Francis Fellowship Program. American Thoracic Society. University of California, San Francisco. University of California, San Francisco. Ernest S. Bazley Grant

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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