Behavior Genetics

, Volume 43, Issue 2, pp 168–176 | Cite as

Comparison of Whole-Genome DNA Methylation Patterns in Whole Blood, Saliva, and Lymphoblastoid Cell Lines

  • Tara M. Thompson
  • Duaa Sharfi
  • Maria Lee
  • Carolyn M. Yrigollen
  • Oksana Yu Naumova
  • Elena L. Grigorenko
Brief Communication


Epigenetic mechanisms, including DNA methylation, that underlie neuropsychiatric conditions have become a promising area of research. Most commonly used DNA sources in such studies are peripheral (whole) blood (WB), saliva (SL), and lymphoblastoid cell lines (LCLs); thus, the question of the consistency of DNA methylation patterns in those cells is of particular interest. To investigate this question we performed comparative analyses of methylation patterns in WB, SL, and LCLs derived from the same individuals, using Illumina HumanMethylation27 BeadChip arrays. Our results showed that DNA methylation patterns in SL are relatively consistent with those in WB, whereas the patterns in LCLs are similarly distinct from both WB and SL. The results indicated that due to multiple random and directed changes in DNA methylation throughout cell culturing, LCLs are not a reliable source of DNA for epigenetic studies and should be used with caution when investigating epigenetic mechanisms underlying biological processes.


Lymphoblastoid cell lines Saliva Whole blood DNA methylation Methylation pattern 



This work was supported by Awards DC007665 as administered by the National Institute of Deafness and Communication Disorders, P50 HD052120 as administered by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Grant R25HL088730 (BioSTEP) from NIH-National Heart, Lung, and Blood Institute. Grantees undertaking such projects are encouraged to freely express their professional judgment. Therefore, this article does not necessarily reflect the position or policies of the National Institutes of Health, and no official endorsement should be inferred. The authors alone are responsible for the content and writing of the article.

Supplementary material

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  1. Abdolmaleky HM, Smith CL, Faraone SV, Shafa R, Stone W, Glatt SJ, Tsuang MT (2004) Methylomics in psychiatry: modulation of gene–environment interactions may be through DNA methylation. Am J Med Genet 127B:51–59PubMedCrossRefGoogle Scholar
  2. Abdolmaleky HM, Zhou JR, Thiagalingam S, Smith CL (2008) Epigenetic and pharmacoepigenomic studies of major psychoses and potentials for therapeutics. Pharmacogenomics 9:1809–1823PubMedCrossRefGoogle Scholar
  3. Brennan EP, Ehrich M, Brazil DP, Crean JK, Murphy M, Sadlier DM et al (2009) Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines. Epigenetics 4:159–164PubMedCrossRefGoogle Scholar
  4. Calıskan M, Cusanovich DA, Ober C, Gilad Y (2011) The effects of EBV transformation on gene expression levels and methylation profiles. Hum Mol Genet 20:1643–1652PubMedCrossRefGoogle Scholar
  5. Dennis GJ, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3PubMedCrossRefGoogle Scholar
  6. Feng J, Fan G (2009) The role of DNA methylation in the central nervous system and neuropsychiatric disorders. Int Rev Neurobiol 89:67–84PubMedCrossRefGoogle Scholar
  7. Fujita S, Buziba N, Kumatori A, Senba M, Yamaguchi A, Toriyama K (2004) Early stage of Epstein-Barr virus lytic infection leading to the “starry sky” pattern formation in endemic Burkitt lymphoma. Arch Pathol Lab Med 128:549–552PubMedGoogle Scholar
  8. Grafodatskaya D, Choufani S, Ferreira JC, Butcher DT, Lou Y, Zhao C et al (2010) EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines. Genomics 95:73–83PubMedCrossRefGoogle Scholar
  9. Hsieh J, Elisch AJ (2010) Epigenetics, hippocampal neurogenesis, and neuropsychiatric disorders: unraveling the genome to understand the mind. Neurobiol Dis 39:73–84PubMedCrossRefGoogle Scholar
  10. Hu VW, Frank BC, Heine S, Lee NH, Quakenbush J (2006) Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics 7:118PubMedCrossRefGoogle Scholar
  11. Huang DW, Sherman BT, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRefGoogle Scholar
  12. Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T (2004) Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol Psychiatry 9:406–416PubMedCrossRefGoogle Scholar
  13. Kaminsky ZA, Tang T, Wang SC, Ptak C, Oh GH, Wong AH et al (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245PubMedCrossRefGoogle Scholar
  14. Laird PW (2003) The power and promise of DNA methylation markers. Nat Rev Cancer 3:253–266PubMedCrossRefGoogle Scholar
  15. Liu J, Morgan M, Hutchison K, Calhoun VD (2010) A study of the influence of sex on genome wide methylation. PLoS ONE 5(4):e10028PubMedCrossRefGoogle Scholar
  16. Maeda E, Akahane M, Kiryu S (2009) Spectrum of Epstein-Barr virus-related diseases: a pictorial review. Jpn J Radiol 27:4–19PubMedCrossRefGoogle Scholar
  17. Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L et al (2008) Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet 82:696–711PubMedCrossRefGoogle Scholar
  18. Mosialos G (2001) Cytokine signaling and EBV cell transformation. Cytokine Growth Factor Rev 12:259–270PubMedCrossRefGoogle Scholar
  19. Neitzel H (1986) A routine method for the establishment of permanent growing lymphoblastoid cell lines. Hum Genet 73:320–326PubMedCrossRefGoogle Scholar
  20. Nguyen A, Rauch TA, Pfeifer GP, Hu VW (2010) Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J 24:3036–3051PubMedCrossRefGoogle Scholar
  21. Nohesara S, Ghadirivasfi M, Mostafavi S, Eskandari M-R, Ahmadkhaniha H, Thiagalingam S, Abdolmaleky HM (2011) DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. J Psychiatr Res 45:1432–1438PubMedCrossRefGoogle Scholar
  22. Sapienza C, Lee J, Powell J, Erinle O, Yafai F, Reichert J et al (2011) DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics 6:20–28PubMedCrossRefGoogle Scholar
  23. Sugawara H, Iwamoto K, Bundo M, Ueda J, Ishigooka J, Kato T (2011) Comprehensive DNA methylation analysis of human peripheral blood leukocytes and lymphoblastoid cell lines. Epigenetics 6:508–515PubMedCrossRefGoogle Scholar
  24. Sun YV, Turner ST, Smith JA, Hammond PI, Lazarus A, Van De Rostyne JL et al (2010) Comparison of the DNA methylation profiles of human peripheral blood cells and transformed B-lymphocytes. Hum Genet 127:651–658PubMedCrossRefGoogle Scholar
  25. Tierling S, Souren NY, Reither S, Zang KD, Meng-Hentschel J, Leitner D et al (2011) DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome. Clin Genet 79:546–553PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Tara M. Thompson
    • 1
  • Duaa Sharfi
    • 1
    • 2
  • Maria Lee
    • 1
  • Carolyn M. Yrigollen
    • 1
    • 3
  • Oksana Yu Naumova
    • 1
    • 4
  • Elena L. Grigorenko
    • 1
    • 5
    • 6
    • 7
  1. 1.Yale UniversityNew HavenUSA
  2. 2.University of IllinoisChicagoUSA
  3. 3.University of CaliforniaDavisUSA
  4. 4.Vavilov Institute of General Genetics of the Russian Academy of SciencesMoscowRussian Federation
  5. 5.Moscow State University for Psychology and EducationMoscowRussian Federation
  6. 6.Columbia UniversityNew YorkUSA
  7. 7.Child Study Center, Department of Psychology, Department of Epidemiology and Public HealthYale UniversityNew HavenUSA

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