Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts

Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie; Hur, Yoon Mi; Ullemar, Vilhelmina; Almqvist, Catarina; Magnusson, Patrik K. E.; Willemsen, Gonneke; Bartels, Meike; Beijsterveldt, Catharina Em van; Bogl, Leonie H.; Pietiläinen, Kirsi H.; Vuoksimaa, Eero; Ji, Fuling; Feng, Na; Pang, Zengchang; Nelson, Tracy L.; Whitfield, Keith E.; Rebato, Esther; Llewellyn, Clare; Fisher, Abigail; Bayasgalan, Gombojav; Danshiitsoodol, Narandalai; Bjerregaard-Andersen, Morten; Beck‐Nielsen, Henning; Sodemann, Morten; Tárnoki, Ádám Domonkos; Tárnoki, Dávid László; Ooki, Syuichi; Stazi, Maria A.; Fagnani, Corrado; Brescianini, Sonia; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Cutler, Tessa L.; Hopper, John L.; Krueger, Robert F.; Pahlen, Shandell; Craig, Jeffrey M.; Saffery, Richard; Haworth, Claire M. A.; Plomin, Robert; Knafo‐Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S. Alexandra; Klump, Kelly L.; Vlietinck, Robert; Derom, Cathérine; Loos, Ruth J.F.; Boomsma, Dorret I.; Sørensen, Thorkild I A; Kaprio, Jaakko; Silventoinen, Karri

doi:10.1038/s41598-018-24634-2

Cited by 22 publications

(24 citation statements)

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“…We found that females from opposite-sex twin pairs did not differ in terms of reproductive outcomes from females from same-sex twins, rather, they had the same chances of getting pregnant and having children compared to women with a female co-twin. In accordance with other studies, baseline characteristics such as birthweight of female twins and their adult BMI were not different between opposite-sex and same-sex twin pairs ( Bogl et al , 2017 ; Jelenkovic et al , 2018 ). Overall, our findings agree with what Medland et al (2008) reported in a study using three cohorts (Australia, The Netherlands and USA) and evaluating a total of 1979 females from same-sex twin pairs and 913 females from opposite-sex twin pairs.…”

Section: Discussionsupporting

confidence: 92%

Testing the twin testosterone transfer hypothesis—intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

et al. 2020

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STUDY QUESTION Does having a male co-twin influence the female twin’s reproductive outcomes? SUMMARY ANSWER Women with a male co-twin had the same chances of being pregnant and having children compared to same-sex twin pairs. WHAT IS KNOWN ALREADY According 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, DURATION This 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, METHODS Fertility 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 CHANCE There 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 CAUTION The 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 FINDINGS Despite 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 NUMBER N/A

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Section: Discussionsupporting

confidence: 92%

Testing the twin testosterone transfer hypothesis—intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

et al. 2020

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“…However, our data did not support these effects for anthropometric traits. When we studied the sex of the co-twin, we found that boys having a female co-twin had a slightly greater birthweight and longer gestational age than DZ boys having a same-sex co-twin; in girls, no differences were seen between opposite-sex and same-sex DZ twins (Jelenkovic et al, 2018b). In adulthood, both men and women having an opposite-sex co-twin were slightly taller than those DZ twins having a same-sex co-twin, whereas BMI showed no differences between these twin-type groups (Bogl et al, 2017).…”

Section: Current Status Of the Databasementioning

confidence: 91%

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

et al. 2019

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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

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“…However, if the correlation in opposite-sex DZ twin pairs is significantly lower than that of the same-sex pairs, the same genes do not contribute to the trait in males and females 5. Data from opposite sex twin pairs have been used as evidence for within utero "testosterone transfer" 334297 for some phenotypes such as epilepsy98 and language impairment 99. However, meta analyses of phenotypes such as body mass index and height have not supported the impact of prenatal hormone exposure on these phenotypes in later life.…”

mentioning

confidence: 99%

Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders

Merikangas

Almasy

2020

Genes Brain and Behavior

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Many neuropsychiatric disorders exhibit differences in prevalence, age of onset, symptoms or course of illness between males and females. For the most part, the origins of these differences are not well understood. In this article, we provide an overview of sex differences in psychiatric disorders including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), anxiety, depression, alcohol and substance abuse, schizophrenia, eating disorders and risk of suicide. We discuss both genetic and nongenetic mechanisms that have been hypothesized to underlie these differences, including ascertainment bias, environmental stressors, X-or Ylinked risk loci, and differential liability thresholds in males and females. We then review the use of twin, family and genome-wide association approaches to study potential genetic mechanisms of sex differences and the extent to which these designs have been employed in studies of psychiatric disorders. We describe the utility of genetic epidemiologic study designs, including classical twin and family studies, large-scale studies of population registries, derived recurrence risks, and molecular genetic analyses of genome-wide variation that may enhance our understanding sex differences in neuropsychiatric disorders.

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Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts

Cited by 22 publications

References 32 publications

Testing the twin testosterone transfer hypothesis—intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

Testing the twin testosterone transfer hypothesis—intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders

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