title: Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures.
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.
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States.
authors.forename: Joshua M
authors.identifier: 0000-0002-2561-6384
authors.initials: JM
authors.lastname: Galanter
authors.affiliation: Department of Genetics, Stanford University, Stanford, United States.
authors.forename: Christopher R
authors.identifier: 0000-0001-9728-6567
authors.initials: CR
authors.lastname: Gignoux
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States.
authors.forename: Sam S
authors.identifier: 0000-0002-2815-6037
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States.
authors.forename: Dara
authors.initials: D
authors.lastname: Torgerson
authors.affiliation: Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Maria
authors.identifier: 0000-0003-0332-437X
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.
authors.forename: Neeta
authors.identifier: 0000-0001-6126-6601
authors.initials: N
authors.lastname: Thakur
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Farber
authors.affiliation: Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Kaiser Permanente-Vallejo Medical Center, Vallejo, United States.
authors.forename: Emerita
authors.initials: E
authors.lastname: Brigino-Buenaventura
authors.affiliation: Bay Area Pediatrics, Oakland, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: LeNoir
authors.affiliation: Department of Pediatrics, Children's Hospital and Research Center, Oakland, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Meade
authors.affiliation: Jacobi Medical Center, Bronx, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Serebrisky
authors.affiliation: Veterans Caribbean Health System, San Juan, United States.
authors.forename: William
authors.initials: W
authors.lastname: Rodríguez-Cintrón
authors.affiliation: Division of Allergy and Immunology, The Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, United States.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Centro de Neumología Pediátrica, San Juan, United States.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodríguez-Santana
authors.affiliation: Center for Genes, Environment, and Health, Department of Pediatrics, National Jewish Health, Denver, United States.
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.affiliation: Graduate School of Public Health and Health Policy, City University of New York, New York, United States.
authors.forename: Luisa N
authors.initials: LN
authors.lastname: Borrell
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States.
authors.forename: Esteban G
authors.identifier: 0000-0001-7475-2035
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Department of Medicine, University of California, San Francisco, United States.
authors.forename: Noah
authors.initials: N
authors.lastname: Zaitlen
mesh_terms: D019175:DNA Methylation; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D005006:Ethnicity; D006630:Hispanic or Latino; D006801:Humans
keywords: Latinos; chromosomes; epigenetics; ethnicity; genes; human; human biology; medicine; methylation