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Heteropaternal Siblings Misclassified as Dizygotic Twins: A Potential Biasing Factor for Heritability Estimates?

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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.

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Notes

  1. 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.

  2. 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).

  3. A centimorgan is a common measure of genetic linkage (Murray et al. 1994).

  4. Measurement error is also captured by the nonshared environment component.

  5. 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).

  6. All raw twin numbers were rounded to the nearest even number.

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Correspondence to Joseph L. Nedelec.

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Ian A. Silver, Joseph L. Nedelec, Nancy L. Sega, Holly Lonergan declare no conflicts of interest.

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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

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