Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 20, 2026.

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

Joshua M Galanter, Christopher R Gignoux, Sam S Oh and 19 more

eLife · 2017 · CC BY

doi:10.1101/036822

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.

Full text

Its licence does not allow us to show the full text. Read it at PubMed Central:

Read at PubMed Central

References 60

  1. 1.

    Alexander DH, Novembre J, Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome Research. 2009;19:1655-1664.

    Not in our library10.1101/gr.094052.109

  2. 2.

    Baran Y, Pasaniuc B, Sankararaman S, Torgerson DG, Gignoux C, Eng C, Rodriguez-Cintron W, Chapela R, Ford JG, Avila PC, Rodriguez-Santana J, Burchard EG, Halperin E. Fast and accurate inference of local ancestry in Latino populations. Bioinformatics. 2012;28:1359-1367.

    Not in our library10.1093/bioinformatics/bts144

  3. 3.

    Barfield RT, Almli LM, Kilaru V, Smith AK, Mercer KB, Duncan R, Klengel T, Mehta D, Binder EB, Epstein MP, Ressler KJ, Conneely KN. Accounting for population stratification in DNA methylation studies. Genetic Epidemiology. 2014;38:231-241.

    Not in our library10.1002/gepi.21789

  4. 4.

    Barr RG, Avilés-Santa L, Davis SM, Aldrich TK, Gonzalez F, Henderson AG, Kaplan RC, LaVange L, Liu K, Loredo JS, Mendes ES, Ni A, Ries A, Salathe M, Smith LJ. Pulmonary disease and age at immigration among hispanics. results from the hispanic community health study study of latinos. American Journal of Respiratory and Critical Care Medicine. 2016;193:386-395.

    Not in our library10.1164/rccm.201506-1211oc

  5. 5.
    Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus · 2010
    No notice
  6. 6.
    DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines · 2011
    No notice
  7. 7.

    Borghol N, Suderman M, McArdle W, Racine A, Hallett M, Pembrey M, Hertzman C, Power C, Szyf M. Associations with early-life socio-economic position in adult DNA methylation. International Journal of Epidemiology. 2012;41:62-74.

    Not in our library10.1093/ije/dyr147

  8. 8.

    Borrell LN. Racial identity among Hispanics: implications for health and well-being. American Journal of Public Health. 2005;95:379-381.

    Not in our library10.2105/ajph.2004.058172

  9. 9.

    Bryc K, Velez C, Karafet T, Moreno-Estrada A, Reynolds A, Auton A, Hammer M, Bustamante CD, Ostrer H. Colloquium paper: genome-wide patterns of population structure and admixture among Hispanic/Latino populations. PNAS. 2010;107 Suppl 2:8954-8961.

    Not in our library10.1073/pnas.0914618107

  10. 10.

    Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Pérez-Stable EJ, Sheppard D, Risch N. The importance of race and ethnic background in biomedical research and clinical practice. New England Journal of Medicine. 2003;348:1170-1175.

    Not in our library10.1056/nejmsb025007

  11. 11.

    Chambers JC, Loh M, Lehne B, Drong A, Kriebel J, Motta V, Wahl S, Elliott HR, Rota F, Scott WR, Zhang W, Tan ST, Campanella G, Chadeau-Hyam M, Yengo L, Richmond RC, Adamowicz-Brice M, Afzal U, Bozaoglu K, Mok ZY, Ng HK, Pattou F, Prokisch H, Rozario MA, Tarantini L, Abbott J, Ala-Korpela M, Albetti B, Ammerpohl O, Bertazzi PA, Blancher C, Caiazzo R, Danesh J, Gaunt TR, de Lusignan S, Gieger C, Illig T, Jha S, Jones S, Jowett J, Kangas AJ, Kasturiratne A, Kato N, Kotea N, Kowlessur S, Pitkäniemi J, Punjabi P, Saleheen D, Schafmayer C, Soininen P, Tai ES, Thorand B, Tuomilehto J, Wickremasinghe AR, Kyrtopoulos SA, Aitman TJ, Herder C, Hampe J, Cauchi S, Relton CL, Froguel P, Soong R, Vineis P, Jarvelin MR, Scott J, Grallert H, Bollati V, Elliott P, McCarthy MI, Kooner JS. Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study. The Lancet Diabetes & Endocrinology. 2015;3:526-534.

    Not in our library10.1016/s2213-8587(15)00127-8

  12. 12.

    Chen W, Boutaoui N, Brehm JM, Han YY, Schmitz C, Cressley A, Acosta-Pérez E, Alvarez M, Colón-Semidey A, Baccarelli AA, Weeks DE, Kolls JK, Canino G, Celedón JC. ADCYAP1R1 and asthma in Puerto Rican children. American Journal of Respiratory and Critical Care Medicine. 2013;187:584-588.

    Not in our library10.1164/rccm.201210-1789oc

  13. 13.

    Cooper RS, Kaufman JS, Ward R. Race and genomics. New England Journal of Medicine. 2003;348:1166-1170.

    Not in our library10.1056/nejmsb022863

  14. 14.
    Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis · 2010
    No notice
  15. 15.

    Evans GW, Kantrowitz E. Socioeconomic status and health: the potential role of environmental risk exposure. Annual Review of Public Health. 2002;23:303-331.

    Not in our library10.1146/annurev.publhealth.23.112001.112349

  16. 16.

    Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics. 2012;13:97-109.

    Not in our library10.1038/nrg3142

  17. 17.

    Florez JC, Price AL, Campbell D, Riba L, Parra MV, Yu F, Duque C, Saxena R, Gallego N, Tello-Ruiz M, Franco L, Rodríguez-Torres M, Villegas A, Bedoya G, Aguilar-Salinas CA, Tusié-Luna MT, Ruiz-Linares A. Strong Association of Socioeconomic Status and Genetic Ancestry in Latinos: Implications for Admixture Studies of Type 2 Diabetes. Racial Identities, Genetic Ancestry, and Health in South America. 2011;137-153.

    Not in our library10.1057/9781137001702_7

  18. 18.
    Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas · 2012
    No notice
  19. 19.

    Galanter JM, Gignoux CR, Torgerson DG, Roth LA, Eng C, Oh SS, Nguyen EA, Drake KA, Huntsman S, Hu D, Sen S, Davis A, Farber HJ, Avila PC, Brigino-Buenaventura E, LeNoir MA, Meade K, Serebrisky D, Borrell LN, Rodríguez-Cintrón W, Estrada AM, Mendoza KS, Winkler CA, Klitz W, Romieu I, London SJ, Gilliland F, Martinez F, Bustamante C, Williams LK, Kumar R, Rodríguez-Santana JR, Burchard EG. Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study. Journal of Allergy and Clinical Immunology. 2014;134:295-305.

    Not in our library10.1016/j.jaci.2013.08.055

  20. 20.

    González Burchard E, Borrell LN, Choudhry S, Naqvi M, Tsai HJ, Rodriguez-Santana JR, Chapela R, Rogers SD, Mei R, Rodriguez-Cintron W, Arena JF, Kittles R, Perez-Stable EJ, Ziv E, Risch N. Latino populations: a unique opportunity for the study of race, genetics, and social environment in epidemiological research. American Journal of Public Health. 2005;95:2161-2168.

    Not in our library10.2105/ajph.2005.068668

  21. 21.

    Grafodatskaya D, Choufani S, Ferreira JC, Butcher DT, Lou Y, Zhao C, Scherer SW, Weksberg R. EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines. Genomics. 2010;95:73-83.

    Not in our library10.1016/j.ygeno.2009.12.001

  22. 22.

    Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. American Journal of Respiratory and Critical Care Medicine. 1999;159:179-187.

    Not in our library10.1164/ajrccm.159.1.9712108

  23. 23.

    Hernandez RD, Kelley JL, Elyashiv E, Melton SC, Auton A, McVean G, Sella G, Przeworski M, 1000 Genomes Project. Classic selective sweeps were rare in recent human evolution. Science. 2011;331:920-924.

    Not in our library10.1126/science.1198878

  24. 24.

    Ho SM, Johnson A, Tarapore P, Janakiram V, Zhang X, Leung YK. Environmental epigenetics and its implication on disease risk and health outcomes. ILAR Journal. 2012;53:289-305.

    Not in our library10.1093/ilar.53.3-4.289

  25. 25.

    Hoffmann TJ, Zhan Y, Kvale MN, Hesselson SE, Gollub J, Iribarren C, Lu Y, Mei G, Purdy MM, Quesenberry C, Rowell S, Shapero MH, Smethurst D, Somkin CP, Van den Eeden SK, Walter L, Webster T, Whitmer RA, Finn A, Schaefer C, Kwok PY, Risch N. Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm. Genomics. 2011;98:422-430.

    Not in our library10.1016/j.ygeno.2011.08.007

  26. 26.
    DNA methylation arrays as surrogate measures of cell mixture distribution · 2012
    No notice
  27. 27.

    Jiang R, Jones MJ, Sava F, Kobor MS, Carlsten C. Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics. Particle and Fibre Toxicology. 2014;11:71.

    Not in our library10.1186/s12989-014-0071-3

  28. 28.

    Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, Reese SE, Markunas CA, Richmond RC, Xu CJ, Küpers LK, Oh SS, Hoyo C, Gruzieva O, Söderhäll C, Salas LA, Baïz N, Zhang H, Lepeule J, Ruiz C, Ligthart S, Wang T, Taylor JA, Duijts L, Sharp GC, Jankipersadsing SA, Nilsen RM, Vaez A, Fallin MD, Hu D, Litonjua AA, Fuemmeler BF, Huen K, Kere J, Kull I, Munthe-Kaas MC, Gehring U, Bustamante M, Saurel-Coubizolles MJ, Quraishi BM, Ren J, Tost J, Gonzalez JR, Peters MJ, Håberg SE, Xu Z, van Meurs JB, Gaunt TR, Kerkhof M, Corpeleijn E, Feinberg AP, Eng C, Baccarelli AA, Benjamin Neelon SE, Bradman A, Merid SK, Bergström A, Herceg Z, Hernandez-Vargas H, Brunekreef B, Pinart M, Heude B, Ewart S, Yao J, Lemonnier N, Franco OH, Wu MC, Hofman A, McArdle W, Van der Vlies P, Falahi F, Gillman MW, Barcellos LF, Kumar A, Wickman M, Guerra S, Charles MA, Holloway J, Auffray C, Tiemeier HW, Smith GD, Postma D, Hivert MF, Eskenazi B, Vrijheid M, Arshad H, Antó JM, Dehghan A, Karmaus W, Annesi-Maesano I, Sunyer J, Ghantous A, Pershagen G, Holland N, Murphy SK, DeMeo DL, Burchard EG, Ladd-Acosta C, Snieder H, Nystad W, Koppelman GH, Relton CL, Jaddoe VW, Wilcox A, Melén E, London SJ. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. The American Journal of Human Genetics. 2016;98:680-696.

    Not in our library10.1016/j.ajhg.2016.02.019

  29. 29.
    450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy · 2012
    No notice
  30. 30.

    Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Mateo Leach I, Drong AW, Abbott J, Wahl S, Tan ST, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor CC, Kleber ME, Li H, Mok ZY, Nakatochi M, Sapari NS, Saxena R, Stewart AF, Stolk L, Tabara Y, Teh AL, Wu Y, Wu JY, Zhang Y, Aits I, Da Silva Couto Alves A, Das S, Dorajoo R, Hopewell JC, Kim YK, Koivula RW, Luan J, Lyytikäinen LP, Nguyen QN, Pereira MA, Postmus I, Raitakari OT, Bryan MS, Scott RA, Sorice R, Tragante V, Traglia M, White J, Yamamoto K, Zhang Y, Adair LS, Ahmed A, Akiyama K, Asif R, Aung T, Barroso I, Bjonnes A, Braun TR, Cai H, Chang LC, Chen CH, Cheng CY, Chong YS, Collins R, Courtney R, Davies G, Delgado G, Do LD, Doevendans PA, Gansevoort RT, Gao YT, Grammer TB, Grarup N, Grewal J, Gu D, Wander GS, Hartikainen AL, Hazen SL, He J, Heng CK, Hixson JE, Hofman A, Hsu C, Huang W, Husemoen LL, Hwang JY, Ichihara S, Igase M, Isono M, Justesen JM, Katsuya T, Kibriya MG, Kim YJ, Kishimoto M, Koh WP, Kohara K, Kumari M, Kwek K, Lee NR, Lee J, Liao J, Lieb W, Liewald DC, Matsubara T, Matsushita Y, Meitinger T, Mihailov E, Milani L, Mills R, Mononen N, Müller-Nurasyid M, Nabika T, Nakashima E, Ng HK, Nikus K, Nutile T, Ohkubo T, Ohnaka K, Parish S, Paternoster L, Peng H, Peters A, Pham ST, Pinidiyapathirage MJ, Rahman M, Rakugi H, Rolandsson O, Rozario MA, Ruggiero D, Sala CF, Sarju R, Shimokawa K, Snieder H, Sparsø T, Spiering W, Starr JM, Stott DJ, Stram DO, Sugiyama T, Szymczak S, Tang WH, Tong L, Trompet S, Turjanmaa V, Ueshima H, Uitterlinden AG, Umemura S, Vaarasmaki M, van Dam RM, van Gilst WH, van Veldhuisen DJ, Viikari JS, Waldenberger M, Wang Y, Wang A, Wilson R, Wong TY, Xiang YB, Yamaguchi S, Ye X, Young RD, Young TL, Yuan JM, Zhou X, Asselbergs FW, Ciullo M, Clarke R, Deloukas P, Franke A, Franks PW, Franks S, Friedlander Y, Gross MD, Guo Z, Hansen T, Jarvelin MR, Jørgensen T, Jukema JW, Kähönen M, Kajio H, Kivimaki M, Lee JY, Lehtimäki T, Linneberg A, Miki T, Pedersen O, Samani NJ, Sørensen TI, Takayanagi R, Toniolo D, Ahsan H, Allayee H, Chen YT, Danesh J, Deary IJ, Franco OH, Franke L, Heijman BT, Holbrook JD, Isaacs A, Kim BJ, Lin X, Liu J, März W, Metspalu A, Mohlke KL, Sanghera DK, Shu XO, van Meurs JB, Vithana E, Wickremasinghe AR, Wijmenga C, Wolffenbuttel BH, Yokota M, Zheng W, Zhu D, Vineis P, Kyrtopoulos SA, Kleinjans JC, McCarthy MI, Soong R, Gieger C, Scott J, Teo YY, He J, Elliott P, Tai ES, van der Harst P, Kooner JS, Chambers JC, BIOS-consortium, CARDIo GRAMplusCD, LifeLines Cohort Study, InterAct Consortium. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nature Genetics. 2015;47:1282-1293.

    Not in our library10.1038/ng.3405

  31. 31.

    Kulis M, Esteller M. DNA methylation and cancer. Advances in Genetics. 2010;70:27-56.

    Not in our library10.1016/b978-0-12-380866-0.60002-2

  32. 32.

    Kumar R, Seibold MA, Aldrich MC, Williams LK, Reiner AP, Colangelo L, Galanter J, Gignoux C, Hu D, Sen S, Choudhry S, Peterson EL, Rodriguez-Santana J, Rodriguez-Cintron W, Nalls MA, Leak TS, O'Meara E, Meibohm B, Kritchevsky SB, Li R, Harris TB, Nickerson DA, Fornage M, Enright P, Ziv E, Smith LJ, Liu K, Burchard EG. Genetic ancestry in lung-function predictions. New England Journal of Medicine. 2010;363:321-330.

    Not in our library10.1056/nejmoa0907897

  33. 33.

    Lam LL, Emberly E, Fraser HB, Neumann SM, Chen E, Miller GE, Kobor MS. Factors underlying variable DNA methylation in a human community cohort. PNAS. 2012;109 Suppl 2:17253-17260.

    Not in our library10.1073/pnas.1121249109

  34. 34.

    Lardenoije R, Iatrou A, Kenis G, Kompotis K, Steinbusch HW, Mastroeni D, Coleman P, Lemere CA, Hof PR, van den Hove DL, Rutten BP. The epigenetics of aging and neurodegeneration. Progress in Neurobiology. 2015;131:21-64.

    Not in our library10.1016/j.pneurobio.2015.05.002

  35. 35.

    Leng S, Liu Y, Thomas CL, Gauderman WJ, Picchi MA, Bruse SE, Zhang X, Flores KG, Van Den Berg D, Stidley CA, Gilliland FD, Belinsky SA. Native American ancestry affects the risk for gene methylation in the lungs of Hispanic smokers from New Mexico. American Journal of Respiratory and Critical Care Medicine. 2013;188:1110-1116.

    Not in our library10.1164/rccm.201305-0925oc

  36. 36.

    Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, Shchetynsky K, Scheynius A, Kere J, Alfredsson L, Klareskog L, Ekström TJ, Feinberg AP. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nature Biotechnology. 2013;31:142-147.

    Not in our library10.1038/nbt.2487

  37. 37.

    Michels KB, Binder AM, Dedeurwaerder S, Epstein CB, Greally JM, Gut I, Houseman EA, Izzi B, Kelsey KT, Meissner A, Milosavljevic A, Siegmund KD, Bock C, Irizarry RA. Recommendations for the design and analysis of epigenome-wide association studies. Nature Methods. 2013;10:949-955.

    Not in our library10.1038/nmeth.2632

  38. 38.

    Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV, Acuña-Alonzo V, Sandoval K, Eng C, Romero-Hidalgo S, Ortiz-Tello P, Robles V, Kenny EE, Nuño-Arana I, Barquera-Lozano R, Macín-Pérez G, Granados-Arriola J, Huntsman S, Galanter JM, Via M, Ford JG, Chapela R, Rodriguez-Cintron W, Rodríguez-Santana JR, Romieu I, Sienra-Monge JJ, del Rio Navarro B, London SJ, Ruiz-Linares A, Garcia-Herrera R, Estrada K, Hidalgo-Miranda A, Jimenez-Sanchez G, Carnevale A, Soberón X, Canizales-Quinteros S, Rangel-Villalobos H, Silva-Zolezzi I, Burchard EG, Bustamante CD. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science. 2014;344:1280-1285.

    Not in our library10.1126/science.1251688

  39. 39.

    Nalls MA, Wilson JG, Patterson NJ, Tandon A, Zmuda JM, Huntsman S, Garcia M, Hu D, Li R, Beamer BA, Patel KV, Akylbekova EL, Files JC, Hardy CL, Buxbaum SG, Taylor HA, Reich D, Harris TB, Ziv E. Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies. The American Journal of Human Genetics. 2008;82:81-87.

    Not in our library10.1016/j.ajhg.2007.09.003

  40. 40.

    Nguyen AB, Moser R, Chou WY. Race and health profiles in the United States: an examination of the social gradient through the 2009 CHIS adult survey. Public Health. 2014;128:1076-1086.

    Not in our library10.1016/j.puhe.2014.10.003

All 60 references

Cited by papers we hold 8

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.