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. Borrell; Esteban G. Burchard; Noah Zaitlen

doi:10.7554/eLife.20532

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

Pediatrics

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	e20532
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.20532
State	Published - 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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10.7554/eLife.20532

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Galanter, J. M., Gignoux, C. R., Oh, S. S., Torgerson, D., Pino-Yanes, M., Thakur, N., Eng, C., Hu, D., Huntsman, S., Farber, H. J., Avila, P. C., Brigino-Buenaventura, E., Lenoir, M. A., Meade, K., Serebrisky, D., Rodríguez-Cintrón, W., Kumar, R., Rodríguez-Santana, J. R., Seibold, M. A., ... Zaitlen, N. (2017). Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. eLife, 6, Article e20532. https://doi.org/10.7554/eLife.20532

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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.",

author = "Galanter, {Joshua M.} and Gignoux, {Christopher R.} and Oh, {Sam S.} and Dara Torgerson and Maria Pino-Yanes and Neeta Thakur and Celeste Eng and Donglei Hu and Scott Huntsman and Farber, {Harold J.} and Avila, {Pedro C.} and Emerita Brigino-Buenaventura and Lenoir, {Michael A.} and Kelly Meade and Denise Serebrisky and William Rodr{\'i}guez-Cintr{\'o}n and Rajesh Kumar and Rodr{\'i}guez-Santana, {Jose R.} and Seibold, {Max A.} and Borrell, {Luisa N.} and Burchard, {Esteban G.} and Noah Zaitlen",

note = "Publisher Copyright: {\textcopyright} Galanter et al.",

year = "2017",

month = jan,

day = "3",

doi = "10.7554/eLife.20532",

language = "English (US)",

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Galanter, JM, Gignoux, CR, Oh, SS, Torgerson, D, Pino-Yanes, M, Thakur, N, Eng, C, Hu, D, Huntsman, S, Farber, HJ, Avila, PC, Brigino-Buenaventura, E, Lenoir, MA, Meade, K, Serebrisky, D, Rodríguez-Cintrón, W, Kumar, R, Rodríguez-Santana, JR, Seibold, MA, Borrell, LN, Burchard, EG & Zaitlen, N 2017, 'Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures', eLife, vol. 6, e20532. https://doi.org/10.7554/eLife.20532

TY - JOUR

T1 - Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

AU - Galanter, Joshua M.

AU - Gignoux, Christopher R.

AU - Oh, Sam S.

AU - Torgerson, Dara

AU - Pino-Yanes, Maria

AU - Thakur, Neeta

AU - Eng, Celeste

AU - Hu, Donglei

AU - Huntsman, Scott

AU - Farber, Harold J.

AU - Avila, Pedro C.

AU - Brigino-Buenaventura, Emerita

AU - Lenoir, Michael A.

AU - Meade, Kelly

AU - Serebrisky, Denise

AU - Rodríguez-Cintrón, William

AU - Kumar, Rajesh

AU - Rodríguez-Santana, Jose R.

AU - Seibold, Max A.

AU - Borrell, Luisa N.

AU - Burchard, Esteban G.

AU - Zaitlen, Noah

PY - 2017/1/3

Y1 - 2017/1/3

N2 - 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.

AB - 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.

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

Abstract

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