Abstract
Heteropaternal superfecundation (HP) occurs when two or more ova are fertilized by sperm from separate males. The resulting siblings are genetically equivalent to half-siblings and share, on average, 25% of their inherited genetic material. In the absence of genetic testing HP siblings could be treated as dizygotic (DZ) twins in behavioral genetic analyses and bias heritability estimates in phenotypic decomposition models. However, the extent to which such misclassification could affect calculated estimates of heritability is currently unknown. Employing simulation analyses, the current study assessed the potential biasing impact across a variety of conditions varying by proportions of DZ twins, sample sizes, and low, moderate, and high levels of genetic and environmental contribution to phenotypic variance. Overall, the results indicated that misclassified HP siblings had minimal impact on estimates of heritability. Nonetheless, greater attention should be paid to the identification of HP siblings within existing and future twin datasets.
Similar content being viewed by others
Notes
The focus of the current study is the misidentification of HP siblings as DZ twins. While it is possible, for example, that same-sex HP siblings could be misidentified as MZ twins it is more likely that they are misidentified as DZ twins, given the phenotypic dissimilarities exhibited by both HP and DZ twins (Segal et al. 2019). Additionally, the misidentification process only applies when DNA sequencing is not employed to identify zygosity.
The accuracy of self-report may depend on the question. Twins’ responses to the question: “Were you and your twin as alike as two peas in a pod?” yielded 98% accuracy, as assessed against blood-typing results across five independent blood group systems; see Cederlöf et al. (1961).
A centimorgan is a common measure of genetic linkage (Murray et al. 1994).
Measurement error is also captured by the nonshared environment component.
When e2 = 0, estimates derived from an ACE model become biased for violating alternative assumptions. To examine the extent to which any potential biasing influence of HP siblings varied across different levels of heritability, supplemental analyses were also conducted (see supplemental material).
All raw twin numbers were rounded to the nearest even number.
References
Barnes JC, Wright JP, Boutwell BB, Schwartz JA, Connolly EJ, Nedelec JL, Beaver KM (2014) Demonstrating the validity of twin research in criminology. Criminology 52:588–626
Berry DP, Bohan A, O’Brien AC, Campion FC, McHugh N, Wall E (2020) Heteropaternal superfecundation frequently occurs in multiple-bearing mob-mated sheep. Anim Genet 51:579–583
Blickstein I (2003) Superfecundation and superfetation: lessons from the past on early human development. J Matern-Fetal Neonatal Med 14:217–219
Borkenau P, Riemann R, Angleitner A, Spinath FM (2002) Similarity of childhood experiences and personality resemblance in monozygotic and dizygotic twins: a test of the equal environments assumption. Personal Individ Differ 33:261–269
Bortolus R, Parazzini F, Chatenoud L, Benzi G, Bianchi MM, Marini A (1999) The epidemiology of multiple births. Hum Reprod Update 5:179–187
Bulbul O, Filoglu G, Altuncul H (2013) Heteropaternal superfecundation: a case report in Turkey. J Fertil 1:112
Cederlöf R, Friberg L, Jonsson E, Kaij L (1961) Studies on similarity diagnosis in twins with the aid of mailed questionnaires. Acta Genetica et Statistica Medica 11:338–362
Conley D, Rauscher E, Dawes C, Magnusson PK, Siegal ML (2013) Heritability and the equal environments assumption: evidence from multiple samples of misclassified twins. Behav Genet 43:415–426
Derks EM, Dolan CV, Boomsma DI (2006) A test of the equal environment assumption (EEA) in multivariate twin studies. Twin Res Hum Genet 9:403–411
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 Genomics Genet 5:1–11
Eaves L, Foley D, Silberg J (2003) Has the “equal environments” assumption been tested in twin studies? Twin Res Hum Genet 6:486–489
García MG, Bolontrade AJ, Penacino GA, Chiesa IJ, Pérez MS (2015) Heteropaternal superfecundation: implicancies in forensic genetics. Forensic Sci Int 5:e633–e635
Girela E, Lorente JA, Alvarez JC, Rodrigo MD, Lorente M, Villanueva E (1997) Indisputable double paternity in dizygous twins. Fertil Steril 67:1159–1161
Hannelius U, Gherman L, Mäkelä VV, Lindstedt A, Zucchelli M, Lagerberg C, Lindgren CM (2007) Large-scale zygosity testing using single nucleotide polymorphisms. Twin Res Hum Genet 10:604–625
Hansen HE, Simonsen BT (2008) A case of heteropaternal superfecundation in a pair of Danish twins. Forensic Sci Int 1:514–515
Harris K, Halpern C, Haberstick B, Smolen A (2013) The National Longitudinal Study of Adolescent Health (Add Health) sibling pairs data. Twin Res Hum Genet 16:391–398
James WH (1993) The incidence of superfecundation and of double paternity in the general population. Acta Geneticae Medicae Et Gemellologiae 42:257–262
Knopik VS, Neiderhiser JM, DeFries JC, Plomin R (2017) Behavioral genetics, 7th edn. Worth Publishers, New York
Lenau F, Hahn E, Peters AL, Gottschling J, Thiel W, Spinath FM (2017) Zygosity determination in twin studies: a validation of zygosity questionnaires using DNA in the German TwinLife Study. TwinLife Work Pap Ser 1:1–13
Liu C, Molenaar PC, Neiderhiser JM (2018) The impact of variation in twin relatedness on estimates of heritability and environmental influences. Behav Genet 48:44–54
Lu H, Wang C, Wu F, Li J (1994) Paternity identification in twins with different fathers. J Forensic Sci 39:1100–1102
Maes HH (2005) ACE Model. In: Everitt B (ed) Encyclopedia of statistics in behavioral science (vol 2). Wiley-Blackwell, Hoboken, pp 5–10
Mahmood HK, Omar AJ, Salih KM (2017) Paternity cases within a medicolegal context: a case study of heteropaternal superfecundation in Iraq. Arab J Forensic Sci Forensic Med 230:1–7
Mogollón F, Casas-Vargas A, Rodrígues F, Usaquén W (2020) Twins from different fathers: a heteropaternal superfecundation case report in Colombia. Biomédica 40:604–608
Murray JC, Buetow KH, Weber JL, Ludwigsen S, Scherpbier-Heddema T, Manion F, Duyk GM (1994) A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC). Science 265:2049–2054
Neale MC, Hunter MD, Pritikin JN, Zahery M, Brick TR, Kirkpatrick RM, Estabrook R, Bates TC, Maes HH, Boker SM (2016) OpenMx 2.0: extended structural equation and statistical modeling. Psychometrika 81:535–549
Nichols RC, Bilbro WC Jr (1966) The diagnosis of twin zygosity. Hum Hered 16:265–275
Reed T, Plassman BL, Tanner CM (2005) Verification of self-report of zygosity determined via DNA testing in a subset of the NAS-NRC twin registry 40 years later. Twin Res Hum Genet 8:362–367
Segal NL, Craig JM, Umstad MP (2019) Challenge to the assumed rarity of heteropaternal superfecundation: findings from a case report. Aust J Forensic Sci 23:1–6
Sun M, Zhang XN, Wu D, Liu QB, Wu YM (2018) A case study of heteropaternal superfecundation in a pair of Chinese twins. Aust J Forensic Sci 50:341–344
Wenk RE, Houtz T, Brooks M, Chiafari FA (1992) How frequent is heteropaternal superfecundation? Acta Geneticae Medicae Et Gemellologiae 41:43–47
Funding
No funds, grants, or other support were received.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Ian A. Silver, Joseph L. Nedelec, Nancy L. Sega, Holly Lonergan declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Edited by Valerie Knopik.
Supplementary information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Silver, I.A., Nedelec, J.L., Segal, N.L. et al. Heteropaternal Siblings Misclassified as Dizygotic Twins: A Potential Biasing Factor for Heritability Estimates?. Behav Genet 51, 137–143 (2021). https://doi.org/10.1007/s10519-020-10039-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10519-020-10039-3