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Revisiting the Children-of-Twins Design: Improving Existing Models for the Exploration of Intergenerational Associations.

ABSTRACT: Datasets comprising twins and their children can be a useful tool for understanding the nature of intergenerational associations between parent and offspring phenotypes. In the present article we explore structural equation models previously used to analyse Children-of-Twins data, highlighting some limitations and considerations. We then present new variants of these models, showing that extending the models to include multiple offspring per parent addresses several of the limitations discussed. Accompanying the updated models, we provide power calculations and demonstrate with application to simulated data. We then apply to intergenerational analyses of height and weight, using a sub-study of the Norwegian Mother and Child Cohort (MoBa); the Intergenerational Transmission of Risk (IToR) project, wherein all kinships in the MoBa data have been identified (a children-of-twins-and-siblings study). Finally, we consider how to interpret the findings of these models and discuss future directions.

SUBMITTER: McAdams TA

PROVIDER: S-EPMC6097723 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Revisiting the Children-of-Twins Design: Improving Existing Models for the Exploration of Intergenerational Associations.

McAdams Tom A TA Hannigan Laurie J LJ Eilertsen Espen Moen EM Gjerde Line C LC Ystrom Eivind E Rijsdijk Fruhling V FV

Behavior genetics 20180630 5

Datasets comprising twins and their children can be a useful tool for understanding the nature of intergenerational associations between parent and offspring phenotypes. In the present article we explore structural equation models previously used to analyse Children-of-Twins data, highlighting some limitations and considerations. We then present new variants of these models, showing that extending the models to include multiple offspring per parent addresses several of the limitations discussed. ...[more]

PMID: 29961153

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Project description:Study questionDoes having a male co-twin influence the female twin's reproductive outcomes?Summary answerWomen with a male co-twin had the same chances of being pregnant and having children compared to same-sex twin pairs.What is known alreadyAccording to the twin testosterone transfer (TTT) hypothesis, in an opposite-sex twin pregnancy, testosterone transfer from the male to the female co-twin occurs. A large body of literature supports the negative impact of prenatal testosterone exposure on female's reproductive health in animal models; however, evidence from human studies remains controversial.Study design, size, durationThis cohort study included all dizygotic female twins in the Aberdeen Maternity and Neonatal Databank (Scotland) born before 1 January 1979. The 317 eligible women were followed up for 40 years for any pregnancies and the outcome of those pregnancies recorded in the same database.Participants/materials, setting, methodsFertility outcomes (number of pregnancies, number of livebirths and age at first pregnancy) were compared between women with a male co-twin (exposed group, n = 151) and those with a female co-twin (unexposed group, n = 166). Population averaged models were used to estimate odds ratios (OR) and 95% CI for all outcomes with adjusting for potential confounders.Main results and the role of chanceThere were no differences in chances of having pregnancies (adj. OR 1.33; 95% CI 0.72, 2.45) and livebirths (adj. OR 1.22; 95% CI 0.68, 2.18) between women from same-sex and opposite-sex twin pairs. Women with a male co-twin were more likely to smoke during pregnancy and, in the unadjusted model, were younger at their first pregnancy (OR 2.13; 95% CI 1.21, 3.75). After adjusting for confounding variables (year of birth and smoking status) the latter finding was no longer significant (OR 1.67; 95% CI 0.90, 3.20).Limitations, reasons for cautionThe dataset was relatively small. For women without a pregnancy recorded in the databank, we assumed that they had not been pregnant.Wider implications of the findingsDespite the evidence from animal studies concerning the adverse effects of prenatal testosterone exposure on female health, our results do not support the TTT hypothesis. The finding that women with a male co-twin are more likely to smoke during pregnancy highlights the importance of considering post-socialisation and social effects in twin studies.Study funding/competing interest(s)European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie project PROTECTED (grant agreement No. 722634) and FREIA project (grant agreement No. 825100). No competing interests.Trial registration numberN/A.

Dataset Information

Revisiting the Children-of-Twins Design: Improving Existing Models for the Exploration of Intergenerational Associations.

Publications

Revisiting the Children-of-Twins Design: Improving Existing Models for the Exploration of Intergenerational Associations.

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