The Impact of Variation in Twin Relatedness on Estimates of Heritability and Environmental Influences

  • Chang Liu
  • Peter C. M. Molenaar
  • Jenae M. Neiderhiser
Original Research

Abstract

By taking advantage of the natural variation in genetic relatedness among identical (monozygotic: MZ) and fraternal (dizygotic: DZ) twins, twin studies are able to estimate genetic and environmental contributions to complex human behaviors. Recently concerns have been raised about the accuracy of twin studies in light of findings of genetic and epigenetic changes in twins. One of the concerns raised is that MZ twins are not 100% genetically and epigenetically similar because they show variations in their genomes and epigenomes leading to inaccurate estimates of heritability. This article presents findings from a simulation study that examined the degree of bias in estimates of heritability and environmentality when the genetic and epigenetic similarity of MZ twins differs from 1.00 and when the genetic and epigenetic similarity of DZ twins differs from 0.50. The findings suggest that in the standard biometric model when MZ or DZ twin similarity differs from 1.00 or 0.50, respectively, the variance that should be attributed to genetic influences is instead attributed to nonshared environmental influences, thus deflating the estimates of genetic influences and inflating the estimates of nonshared environmental influences. Although estimates of genetic and nonshared environmental influences from the standard biometric model were found to deviate from “true” values, the bias was usually smaller than 10% points indicating that the interpretations of findings from previous twin studies are mostly correct.

Keywords

Twin studies Standard biometric model Genetic and epigenetic similarity Heritability estimate Simulation study 

Supplementary material

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Supplementary material 1 (DOCX 55 KB)
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Supplementary material 2 (FOR 6 KB)
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Supplementary material 3 (FOR 7 KB)

References

  1. Baranzini SE, Mudge J, van Velkinburgh JC, Khankhanian P, Khrebtukova I, Miller NA, Kim RW (2010) Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 464(7293):1351–1356. doi: 10.1038/nature08990 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bell JT, Spector TD (2011) A twin approach to unraveling epigenetics. Trends Genet. doi: 10.1016/j.tig.2010.12.005 PubMedPubMedCentralGoogle Scholar
  3. Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, de Ståhl TD, … Poplawski A (2008) Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 82(3):763–771. doi: 10.1016/j.ajhg.2007.12.011 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Burt SA (2009) Rethinking environmental contributions to child and adolescent psychopathology: a meta-analysis of shared environmental influences. Psychol Bull 135(4):608–637. doi: 10.1037/a0015702 CrossRefPubMedGoogle Scholar
  5. Burt CH, Simons RL (2014) Pulling back the curtain on heritability studies: Biosocial criminology in the postgenomic era. Criminology 52(2):223–262. doi: 10.1111/1745-9125.12036 CrossRefGoogle Scholar
  6. Castellani CA, Laufer BI, Melka MG, Diehl EJ, O’Reilly RL, Singh SM (2015) DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks. BMC Med Genom 8(1):1–12. doi: 10.1186/s12920-015-0093-1 CrossRefGoogle Scholar
  7. Castorina, P., Selicorni, A., Bedeschi, F., Dalprà, L., & Larizza, L. (1997). Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome. Am J Med Genet 69(1):107–111. doi: 10.1002/(SICI)1096-8628(19970303)69:1<107::AID-AJMG21>3.0.CO;2-S CrossRefPubMedGoogle Scholar
  8. Charney E (2012) Behavior genetics and postgenomics. Behav Brain Sci 35(05):331–358. doi: 10.1017/S0140525X11002226 CrossRefPubMedGoogle Scholar
  9. Czyz W, Morahan JM, Ebers GC, Ramagopalan SV (2012) Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences. BMC Med 10(1):93. doi:10.1186/1741-7015-10-93 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A, Kane F, Toulopoulou T (2011) Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 20(24):4786–4796. doi: 10.1093/hmg/ddr416 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dickens WT, Flynn JR (2001) Heritability estimates versus large environmental effects: the IQ paradox resolved. Psychol Rev 108(2):346–369. doi: 10.1037/0033-295X.108.2.346 CrossRefPubMedGoogle Scholar
  12. Dolan C, Nivard M, van Dongen J, van der Sluis S, Boomsma D (2015) Methylation as an epigenetic source of random genetic effects in the classical twin design. Adv Genom Genet 5:305–315. doi: 10.2147/AGG.S46909 Google Scholar
  13. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, … Benitez J (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102(30):10604–10609. doi: 10.1073/pnas.0500398102 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128(4):635–638. doi: 10.1016/j.cell.2007.02.006 CrossRefPubMedGoogle Scholar
  15. Gringras P, Chen W (2001) Mechanisms for differences in monozygous twins. Early Hum Dev 64(2):105–117. doi: 10.1016/S0378-3782(01)00171-2 CrossRefPubMedGoogle Scholar
  16. Handel AE, Ebers GC, Ramagopalan SV (2010) Epigenetics: molecular mechanisms and implications for disease. Trends Mol Med 16(1):7–16. doi: 10.1016/j.molmed.2009.11.003 CrossRefPubMedGoogle Scholar
  17. Heijmans BT, Kremer D, Tobi EW, Boomsma DI, Slagboom PE (2007) Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus. Hum Mol Genet 16(5):547–554. doi: 10.1093/hmg/ddm010 CrossRefPubMedGoogle Scholar
  18. Iourov IY, Vorsanova SG, Yurov YB (2006) Chromosomal variation in mammalian neuronal cells: known facts and attractive hypotheses. Int Rev Cytol 249:143–191. doi: 10.1016/S0074-7696(06)49003-3 CrossRefPubMedGoogle Scholar
  19. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33:245–254. doi:10.1038/ng1089 CrossRefPubMedGoogle Scholar
  20. Kaminsky ZA, Tang T, Wang S-C, Ptak C, Oh GH, Wong AH, … Petronis A (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41(2):240–245. doi: 10.1038/ng.286 CrossRefPubMedGoogle Scholar
  21. Klahr AM, Burt SA (2014) Elucidating the etiology of individual differences in parenting: a meta-analysis of behavioral genetic research. Psychol Bull 140(2):544–586. doi: 10.1037/a0034205 CrossRefPubMedGoogle Scholar
  22. Kuratomi G, Iwamoto K, Bundo M, Kusumi I, Kato N, Iwata N, Kato T (2008) Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol Psychiatry 13(4):429–441. doi: 10.1038/sj.mp.4002001 CrossRefPubMedGoogle Scholar
  23. Lerner RM (2004) Genes and the promotion of positive human development: Hereditarian versus developmental systems perspectives. In: Coll CG, Bearer E, Lerner RM (eds) Nature and nurture: The complex interplay of genetic and environmental influences on human behavior and development. Erlbaum, Mahwah, NJ, p. 1–33Google Scholar
  24. Martin SL (2009) Developmental biology: jumping-gene roulette. Nature 460(7259):1087–1088. doi:10.1038/4601087a CrossRefPubMedGoogle Scholar
  25. Miller MB, DeYoung CG, McGue M (2012) Assumptions in studies of heritability and genotype–phenotype association. Behav Brain Sci 35(05):372–373. doi: 10.1017/S0140525X12001380 CrossRefPubMedGoogle Scholar
  26. Molenaar PC, Smit DJ, Boomsma DI, Nesselroade JR (2012) Estimation of subject-specific heritabilities from intra-individual variation: iFACE. Twin Res Hum Genet 15(03):393–400. doi: 10.1017/thg.2012.9 CrossRefPubMedGoogle Scholar
  27. Montier L. L. C., Deng JJ, Bai Y (2009) Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genom 36(3):125–131. doi: 10.1016/S1673-8527(08)60099-5 CrossRefGoogle Scholar
  28. Neiderhiser JM, Reiss D, Pedersen NL, Lichtenstein P, Spotts EL, Hansson K, … Elthammer O (2004) Genetic and environmental influences on mothering of adolescents: a comparison of two samples. Dev Psychol 40(3):335–351. doi: 10.1037/0012-1649.40.3.335 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Ollikainen M, Smith KR, Joo E. J.-H., Ng HK, Andronikos R, Novakovic B, … Craig JM (2010) DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum Mol Genet 19(21):4176–4188. doi: 10.1093/hmg/ddq336 CrossRefPubMedGoogle Scholar
  30. Plomin R, Daniels D (1987) Why are children in the same family so different from one another? Behav Brain Sci 10(01):1–16. doi: 10.1017/S0140525X00055941 CrossRefGoogle Scholar
  31. Plomin R, DeFries JC, Knopik VS, Neiderhiser J (2013) Behavioral genetics. Worth Publishers, New York, NYGoogle Scholar
  32. Plomin R, DeFries JC, Knopik VS, Neiderhiser JM (2016) Top 10 Replicated Findings From Behavioral Genetics. Perspect Psychol Sci 11(1):3–23. doi: 10.1177/1745691615617439 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Polderman TJ, Benyamin B, De Leeuw CA, Sullivan PF, Van Bochoven A, Visscher PM, Posthuma D (2015) Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 47(7):702–709. doi: 10.1038/ng.3285 CrossRefPubMedGoogle Scholar
  34. Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BS, … Anliker B (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25(9):2176–2180. doi: 10.1523/JNEUROSCI.4560-04.2005 CrossRefPubMedGoogle Scholar
  35. Reiss D, Neiderhiser JM, Hetherington EM, Plomin R (2000) The relationship code: deciphering genetic and social influences on adolescent development, vol 1. Harvard University Press, Cambridge, MAGoogle Scholar
  36. Scheet P, Ehli EA, Xiao X, van Beijsterveldt CE, Abdellaoui A, Althoff RR, … Huizenga PE (2012) Twins, tissue, and time: an assessment of SNPs and CNVs. Twin Res Hum Genet 15(06):737–745. doi:10.1017/thg.2012.61 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Singer T, McConnell MJ, Marchetto MC, Coufal NG, Gage FH (2010) LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes? Trends Neurosci 33(8):345–354. doi: 10.1016/j.tins.2010.04.001 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Tsujita T, Niikawa N, Yamashita H, Imamura A, Hamada A, Nakane Y, Okazaki Y (1998) Genomic discordance between monozygotic twins discordant for schizophrenia. Am J Psychiatry 155:422–424. doi: 10.1176/ajp.155.3.422 CrossRefPubMedGoogle Scholar
  39. Turkheimer E (2000) Three laws of behavior genetics and what they mean. Curr Dir Psychol Sci 9(5):160–164. doi: 10.1111/1467-8721.00084 CrossRefGoogle Scholar
  40. Turkheimer E, Waldron M (2000) Nonshared environment: a theoretical, methodological, and quantitative review. Psychol Bull 126(1):78–108. doi: 10.1037/0033-2909.126.1.78 CrossRefPubMedGoogle Scholar
  41. Van Dongen J, Slagboom PE, Draisma HH, Martin NG, Boomsma DI (2012) The continuing value of twin studies in the omics era. Nat Rev Genet 13(9):640–653. doi: 10.1038/nrg3243 CrossRefPubMedGoogle Scholar
  42. Van Dongen J, Nivard MG, Willemsen G, Hottenga J-J, Helmer Q, Dolan CV, … Breeze CE (2016) Genetic and environmental influences interact with age and sex in shaping the human methylome. Nature communications 7:11115. doi: 10.1038/ncomms11115 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Veenma D, Brosens E, de Jong E, van de Ven C, Meeussen C, Cohen-Overbeek T, Tibboel D (2012) Copy number detection in discordant monozygotic twins of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) cohorts. Eur J Hum Genet 20(3):298–304. doi: 10.1038/ejhg.2011.194 CrossRefPubMedGoogle Scholar
  44. Weber-Lehmann J, Schilling E, Gradl G, Richter DC, Wiehler J, Rolf B (2014) Finding the needle in the haystack: differentiating “identical” twins in paternity testing and forensics by ultra-deep next generation sequencing. Forensic Sci Int Genet 9:42–46. doi: 10.1016/j.fsigen.2013.10.015 CrossRefPubMedGoogle Scholar
  45. Wong C. C. Y., Caspi A, Williams B, Craig IW, Houts R, Ambler A, … Mill J (2010) A longitudinal study of epigenetic variation in twins. Epigenetics 5(6):516–526. doi: 10.4161/epi.5.6.12226 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of PsychologyThe Pennsylvania State UniversityUniversity ParkUSA
  2. 2.Department of Human Development and Family StudiesThe Pennsylvania State UniversityUniversity ParkUSA

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