Haldane (J. B. S.) was a brilliant scientist. His 'cost of natural selection' is a view of the dark underbelly of Darwin's creation - a count of the individuals who fall by the wayside when one allele displaces another. Th. Dobzhansky, perhaps not liking Haldane's brand of mathematics, called in the eminent European William Feller to scrutinize Haldane's cost. Feller published two articles (1966, 1967). The second sentence of the first paper shows that Feller misunderstood what Haldane measured: 'These authors [Haldane and M. Kimura] introduce a measure for the loss in population size caused by a slow natural selection.' Feller made intricate calculations of population size under various assumptions. These missed the point of Haldane's clever notion. Feller's two articles are an attempted demolition of conventional population genetics methodology.
Populations of Arab ancestry remain underrepresented in global twin studies. These populations are described by distinct genetic characteristics, high consanguinity, and strong familial relatedness. To contribute to diversity in genetics and twin research, the Qatar Twin Registry (QTR) was established as the first national twin registry in the Arab world and the second in the Middle East and North Africa. The QTR is a prospective and retrospective cohort study developed by Qatar University in collaboration with the Qatar Precision Health Institute (QPHI). The registry integrates with Qatar's national biobank and whole-genome sequencing infrastructure to enable large-scale twin-based research. Participants contribute comprehensive health, developmental, psychosocial, and lifestyle information, along with biological samples collected through clinic-based assessments and home visits. QTR marks a milestone in regional genetic and epidemiological research. Leveraging and linking to Qatar's national biobank and genomic infrastructure, it establishes a sustainable framework for investigating heritability, gene-environment interactions, and complex diseases in an underrepresented Arab population, contributing to global precision medicine efforts.
Twin-to-twin transfusion syndrome (TTTS) affects 10-15% of monochorionic diamniotic (MCDA) twin pregnancies and is associated with high perinatal mortality if left untreated. Selective Fetoscopic Laser Photocoagulation (SFLP) is the current standard of care for advanced-stage TTTS. This retrospective cohort study aimed to assess survival outcomes following SFLP and evaluate the learning curve associated with its implementation. It included 300 MCDA twin pregnancies with TTTS treated by SFLP from October 2018 to December 2024. Patients were chronologically divided into three equal groups (n = 100 per group) based on the order of procedure to assess outcome trends over time. Primary outcome was dual survival at birth; secondary outcomes included survival of at least one fetus, gestational age at delivery, birth weight, and neonatal complications. Multivariable logistic regression was used to assess clinical and procedural factors associated with dual survival, while CUSUM analysis was employed to evaluate the learning curve. Among 300 cases, dual survival was achieved in 57% of pregnancies. In multivariable logistic regression, clinical factors, including Quintero stage, placental orientation, and gestational age, were not significantly associated with outcomes (p > .05). The treatment cohort remained the sole independent predictor of survival, with significantly lower odds of success in Group 1 (OR 0.041; 95% CI [0.004, 0.429]) and Group 2 (OR 0.051; 95% CI [0.005, 0.492]) compared to Group 3 (p < .01). CUSUM analysis demonstrated that procedural competence, defined by sustained adequate survival rates, was achieved after the 141st procedure. This study demonstrates improved survival outcomes in TTTS cases treated with SFLP over time, confirming a significant institutional learning curve. The findings highlight the importance of surgical experience and procedural standardization. In resource-limited settings, establishing structured training and mentorship is essential to optimize outcomes and safely expand access to fetal therapy.
The functional significance of monozygotic and dizygotic twinning is explored. The specific question of why twinning is maintained in human populations, despite the risks to mothers and infants, will be addressed. Next, summaries of recent and current research will be presented. The topics cover congenital chimerism, parental favoritism toward one twin, parasitic twins, and a twin study of primal world beliefs. In the final section of this essay a variety of informative general interest stories are considered. They include twins' matching lives; the birth of three triplet sets; a pair of Chinese reared-apart twins; and a landmark conjoined twin separation.
To accompany the publication of the special issue, 'Population-Level Data Linkages in Worldwide Twin Registries', an online, interactive tool titled 'Twin Registries Worldwide' has been developed to provide an overview of twin registries across the globe. The tool currently offers a searchable table view that allows users to explore twin registries by country, registry name, recruitment period, sample size, phenotypic domains, availability of biological samples, and linkage to administrative or health-related databases.
Establishing causality in nutritional science is difficult. Human diets are complex, and individuals vary substantially in how they respond to dietary exposures. The nutrition literature mostly relies on observational studies, which are vulnerable to confounding and measurement error. Twin-based randomized controlled trials (RCTs), especially the co-twin control design, offer a compelling methodological solution to many of these challenges. This design enables researchers to distinguish genetic from environmental influences on health outcomes. The present scoping review was conducted to systematically map twin RCTs in nutrition science, evaluate their methodological approaches, and identify gaps and opportunities for future research. A comprehensive search across clinical trial registries and electronic databases yielded only 13 eligible studies, demonstrating that co-twin randomized dietary interventions remain rare relative to standard study designs using nontwins or twins assigned to the same arm. The interventions used in these eligible RCTs could be classified into four groups: dietary pattern interventions, nutrient- or supplement-based interventions, dietary component modification, and behavioral or multimodal interventions. This limited number of studies may be explained by recruitment challenges and concerns about generalizability. Greater international collaboration, standardized trial protocols, and integration of emerging technologies could expand the utility of twin designs in nutrition science.
The Hungarian Twin Registry (HTR) has operated as a population-based registry since 2021, following its establishment at Semmelweis University in Budapest. In recent years, the HTR infrastructure has been substantially expanded, including blood storage facilities, information technology systems, a phone bank and voicemail system, and administrative resources. Adult twins (aged ≥18 years) and relatives (parents, foster parents, or caregivers) of twins under 18 years of age can register via the registry's website or by voicemail following a nationwide identification and notification process. The registration questionnaire consists of eight sections covering sociodemographic and anthropometric characteristics, smoking habits, and medical history, including diseases, surgeries, and therapies. By December 20, 2025, a total of 12,676 twin individuals and their parents or guardians had registered, including 7244 adult twins and 5432 parents or guardians of minors. Based on self-reported data, 44.1% of registered adult twins were monozygotic (MZ) and 55.9% dizygotic (DZ), while among registered children 23.5% were MZ and 76.5% DZ. Of the registered adult twins, 68.4% were female. The HTR offers substantial potential for linkage with national health databases, enabling enrichment of phenotypic and outcome data without additional participant burden. In particular, linkage with the Hungarian National Cancer Registry and other health-related databases is feasible under appropriate ethical approval and data protection procedures and may support long-term follow-up and disease-specific analyses. The article also summarizes current research projects conducted within the HTR, which has become the largest population-based twin registry in Central and Eastern Europe based on the number of registrations.
Twin research informs our thinking about possible human reproductive cloning (HRC). Other human models for assessing the benefits and difficulties of HRC are look-alike parent-child and sibling pairs. An in-depth interview with an extraordinary mother-daughter pair is provided. This section is followed by reviews of research on infantile pyknocytosis in a dizygotic (DZ) twin, monozygotic (MZ) twin discordance for hemimicrencephaly, unusual dental development in a twin, and 'gaze fingerprint signatures'. The final section presents human interest stories of identical twin executives at odds, the loss of identical twin Jim Whittaker, identical twin artists, and twin wisdom captured in stone.
The purpose of this cross-sectional study was to investigate knowledge about multiple-birth families among midwives and public health nurses working in maternity and child health clinics in Finland. The data were collected with a Finnish language questionnaire in spring 2022. Because relevant questionnaires did not exist, we created a new questionnaire based on existing knowledge and practices. The questionnaire assessed three themes of multiple-birth knowledge relevant for the target population. The response rate was 50% and the number of respondents was 72. A total of 92 items were assessed and these showed high levels of consistency within themes. The respondents had substantial variation in their levels of multiple-birth family knowledge concerning different themes (Kruskal-Wallis test, p < .001). Post-hoc pairwise comparisons revealed many significant differences between themes, the two themes of knowledge of speech development of twins and breast feeding having the lowest level of knowledge, while interaction and support expected by the parents having the highest level of knowledge. The respondents had good knowledge of only five themes of multiple-birth family knowledge. Of all the themes, only knowledge about breast feeding was not significantly related to other themes, except for a weak correlation (r = .264, p < .05) with knowledge about caring for twins and understanding the situation. The age, educational level and work experience of respondents did not significantly affect their scores (all p > .1). Although the respondents had knowledge about early interaction, bonding and supporting the growth and development of child, its application is insufficient or lacking because of the special needs of multiple birth families. Further research is required on the effectiveness of training interventions and on nursing in different nursing contexts.
Twin studies provide a powerful framework to identify genetic and environmental influences on health and development, particularly during infancy, childhood, and adolescence. Although twin research has expanded globally, evidence from South Asia remains limited and poorly characterized. This systematic review aimed to synthesize health research involving infant, child, and adolescent twins conducted in South Asia and to identify methodological patterns and research gaps relevant to future twin research in the region. A systematic review was conducted according to a registered protocol (PROSPERO: CRD42018105704) using the PICOS framework. Multiple international and regional databases were searched from inception to September 2025. Studies recruiting twins aged 0-19 years within the South Asian Association for Regional Cooperation (SAARC) countries were included. Study selection, data extraction, and quality appraisal were conducted independently, with study quality assessed using Joanna Briggs Institute critical appraisal tools. Results were synthesized narratively due to heterogeneity across study designs and outcomes. Eighteen studies were included from 1245 identified records. Most studies focused on twin pregnancy and neonatal outcomes (61%), followed by dentistry, ocular health, and gut microbiota. Twin pregnancies were consistently associated with increased risks of low birth weight, preterm birth, and perinatal morbidity and mortality. A limited number of studies applied classical twin designs to investigate genetic and environmental contributions. Twin research involving infants, children, and adolescents in South Asia remains limited in scope and methodological depth. Strengthening twin registries, methodological standardization, and collaborations is essential to advance genetically informative research and enhance the global representativeness of twin studies.
The author presents a commentary on the trilogy of papers by Damien Morris entitled 'Behavioral Genetics and Human Agency: How Selectively Deterministic Theories of Free Will Drive Unwarranted Opposition to Behavioral Genetic Research and Undermine Our Moral and Legal Conventions', published recently in this journal [PMID 40457806, 40963213, 41107251]. In addition to commenting on this specific set of papers, the author offers a broader perspective and defense of the field of behavioral genetics.
This study compared mental health problems and psychiatric treatment experiences between mothers of twins and mothers of singletons, controlling for assisted reproductive technology (ART), perceived family support (PFS), and demographic covariates. Participants were 1592 South Korean mothers, including 853 mothers of singletons (M = 36.6 years, SD = 3.6) and 739 mothers of twins (M = 38.3 years, SD = 4.9), who completed an online survey assessing the General Health Questionnaire (GHQ), psychiatric treatment experience (PTE), PFS, ART use, and demographic factors. Hierarchical regression, analysis of covariance (ANCOVA), and logistic regression analyses were conducted with GHQ as the outcome variable. PTE was analyzed both as a dependent variable and as an independent variable. ART use significantly predicted GHQ scores beyond PFS, PTE, and demographics in both groups. After adjusting for all covariates, mothers of twins had higher GHQ scores than mothers of singletons, although the effect size was small (Cohen's d = 0.16). Logistic regression revealed that mothers of twins were more than twice as likely to have received psychiatric treatment compared to mothers of singletons (odds ratio = 2.5, 95% CI [1.8, 3.4]). These results indicate that mothers of twins experience greater mental health challenges than mothers of singletons, indicating the importance of tailored mental health screening, prevention, and intervention programs for this vulnerable group.
The Swedish Twin Registry (STR), established in the late 1950s, is one of the world's most comprehensive twin registries and a cornerstone for research on genetic and environmental determinants of health. STR includes data on Swedish-born twins since 1886, complemented by longitudinal questionnaires, clinical measures, and biobank samples. In 2019, STR became a national research infrastructure with a mission to provide broader data sharing, while in 2025, STR further transitioned into a legally defined role as a 'certain research database' under the new Swedish Act on Certain Research Databases. The new legislation provides a framework for collecting and storing personal data with broad consent for future research projects, without requiring ethical approval for the data collection per se. Instead, ethical review is conducted separately for each research project seeking to use STR data. This article aims to describe STR's current role, governance, and legal context, highlighting implications for data access and biobank integration. The registry currently holds data on more than 160,000 twins, with ongoing ascertainment at 9 months and 9 years with follow-ups at ages 15, 18, and 24. Annual linkages to national health registers enrich longitudinal analyses of disease outcomes. A variable search engine is openly available via STR's web portal while higher level metadata is provided through Swedish research data services. STR's evolution illustrates both opportunities and challenges in balancing open science practices, legal compliance, and participant integrity within large-scale research infrastructures.
Record linkage projects provide powerful opportunities to enrich cohort data with administrative and clinical information from national registries. The Netherlands Twin Register (NTR) is a large population-based twin-family cohort with longitudinal data collection that has established multiple record linkage initiatives to expand research on genetic and environmental determinants of health, disease, behaviour, development, and fertility. In this article we summarize and discuss NTR record linkage projects. Clinical and pathology registries have provided essential data on chorionicity, reproductive history, neonatal thyroid function, and cancer diagnoses, facilitating studies on prenatal environment, disease heritability, and polygenic risk prediction for diseases. Linkage with health insurance data has enabled validation of medication use and health research. Collaborations with Statistics Netherlands allow linkage to nationwide population-based data via secure infrastructures such as Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI), supporting genomewide association studies of, for example, healthcare expenditure. Finally, linkage to environmental exposure datasets has permitted exposomewide analyses of health and wellbeing. Together, these projects illustrate the feasibility, scientific value, and challenges of record linkage in the Dutch context, highlighting its role in advancing twin research, genetic epidemiology, and population health studies.
The Twins Early Development Study (TEDS) is a longitudinal population study of over 10,000 twin pairs born in England and Wales between 1994 and 1996. As the twins enter their thirties, a primary focus of TEDS is to better understand the development of common physical and mental health problems and the relationship with the different social milestones of adulthood (e.g., employment, partnerships, and/or parenthood). With over 30 years of prospectively collected questionnaire and genetic data, the study is uniquely placed to answer questions about the health challenges facing young adults today. Incorporating linked medical records with the existing research data will provide a different data perspective on our twin's health status and outcomes and support more equitable research by helping to address both response and attrition bias. This article provides an overview of the protocol to link TEDS participants to electronic health records collected by the UK National Health Service (NHS). It will outline the linkage process, characterize the available linked study sample and NHS datasets, and describe the legal basis for this work.
Hyperuricemia is a common metabolic disorder and has become a global health concern. This study investigated the association between DNA methylation (DNAm) and serum uric acid (SUA) by conducting an epigenomewide association study (EWAS) in Chinese monozygotic (MZ) twins. Genomewide DNAm of 50 MZ twin pairs was profiled using the Infinium MethylationEPIC v2.0 BeadChip (935K). Generalized estimating equations (GEE) were used to examine the association between DNAm and SUA. Causal relationships between DNAm and SUA were assessed using ICE FALCON approach. Associations between mRNA expression and SUA were further assessed. Finally, candidate genes identified through epigenomewide association study (EWAS), causal inference, and gene expression analyses were validated in a longitudinal twin study. We identified 70 CpGs, mapping to genes such as DOK6 and NGLY1, significantly associated with SUA (Bonferroni correction p < 5.8 × 10-8). Causal analyses revealed one CpG with a causal effect of DNAm on SUA, 22 CpGs with causal effects of SUA on DNAm, and 33 CpGs showing bidirectional causality. Eleven genes displayed expression levels associated with SUA. DOK6, NGLY1, PKM, and SLC44A1 were selected as candidate genes, all of which showed unidirectional causal effect of SUA on DNAm. In the longitudinal analysis, baseline SUA levels (2012-13) were associated with subsequent DNAm levels in DOK6 and NGLY1 genes (2023-24). In conclusion, we found that SUA levels may influence DNAm variations, particularly at CpG loci within the DOK6 and NGLY1 genes. These findings provide key clues for future investigations into the mechanisms linking SUA with its epigenetic regulatory pathways.
This report provides an overview of the current state of the German twin family panel TwinLife, including information on design and sample characteristics as well as a selection of assessed constructs. TwinLife is a register-based longitudinal panel of four birth cohorts of German-speaking monozygotic and dizygotic same-sex twin pairs, and their core family members, including parents and siblings, but also partners and children of twins, if available. Using address data provided by a representative set of residents' registration offices from across Germany, twin families were identified through a multistage process. The twins were born in 1990-1993, 1997-1998, 2003-2004, and 2009-2010. They were about 5, 11, 17, and 23 years old at the time of the first survey. Designed to investigate the development of social inequalities over the life course, the TwinLife currently covers an observation period from 2014 to 2025. In the first wave, the panel included data on 4096 twin families from all parts of Germany, covering the full range of key socioeconomic indicators. Over the years, the core TwinLife project has been expanded by several satellite projects, such as the molecular genetic TwinSNPs and the TwinLife Epigenetic Change Satellite (TECS) project. TwinLife provides a unique database with a wide-ranging potential for research, since it combines a longitudinal panel with an extended twin family design, adding genetic, epigenetic and additional biological data as well as the possibility to match geographical information.
Myopia is an increasing global health concern and a leading cause of visual impairment. Genetic factors play a major role, and polygenic risk scores (PRSs) may help identify children at high risk of developing myopia. However, most PRSs are based on European populations, and accurately predicting risk across ancestries remains a challenge. We developed and evaluated PRSs for spherical equivalent refractive error (SER) and myopia using multitrait and multi‑ancestry genomewide association study data. A multitrait analysis of SER‑correlated traits identified 709 genomewide significant loci. PRSs were generated with SBayesRC for each ancestry group and for a combined multi‑ancestry model, and validated in the Australian Twins Eye Study and non‑European participants from the UK Biobank. The European PRSs explained approximately 20% of SER variance in Europeans and 18% in admixed Europeans and showed good transferability to South Asian (14%), East Asian (13%), and African (8%) groups. A multi‑ancestry PRS further improved prediction in Africans, explaining 9% of the variance. Predictive accuracy for high myopia was strong in the admixed group (AUC = 0.82, 95% CI [0.78, 0.87]), with all ancestry groups achieving AUCs of at least 0.70; European ancestry data were not available. PRS also predicted axial length in children, particularly those aged 5-8 years, where individuals in the lowest 10% of the PRS distribution had significantly longer axial lengths (β = 0.81 mm, p = 5.71 × 10-3). These findings enhance genetic prediction of SER and myopia, showing the potential of multitrait, multi-ancestry PRS for early, equitable risk stratification.
Self-concept in adolescence plays a key role in psychological adjustment, yet its development in twins remains underexplored - especially in Central Europe. While previous studies suggest minor differences between monozygotic (MZ) and dizygotic (DZ) twins, cultural and contextual influences may affect how twins perceive themselves. This mixed-method study examined 336 Czech adolescent twins (168 twin pairs; 32 MZ, 136 DZ) aged 11-15 years. Participants completed three standardized instruments: the Behavioral and Psychological Adjustment Questionnaire (BPQA), the School Performance and Adjustment Scale (SPAS), and the Rosenberg Self-Esteem Scale (RSES). Quantitative analyses included t tests, Analyses of Variance (ANOVAs), and Pearson correlations. To triangulate findings, focus group interviews were conducted with three twin pairs and analyzed thematically. No statistically significant differences were found between MZ and DZ twins across BPQA, SPAS, and RSES measures. However, small, nonsignificant trends suggested slightly higher emotional self-concept scores in MZ twins. A modest gender difference emerged: girls reported more internalizing symptoms. Correlational analysis showed that lower behavioral difficulties were associated with higher school adjustment and self-esteem. Thematic analysis from focus groups confirmed key patterns such as the emotional safety of twinship and the struggle for individuality. Zygosity does not appear to be a major predictor of self-concept in early adolescence. Instead, self-perception in twins is shaped by a complex interplay of mental health, family dynamics, and peer context. Future research should compare twin self-concept development across cultures to further examine sociocultural influences.
The Early Growth and Development Study (EGDS) began in 2002 as a longitudinal prospective adoption study of birth parents, adoptive parents, and adopted children (n = 361 adoptees). It expanded in 2007 to include a second cohort of adoptees (n = 200), and a third cohort of siblings (siblings reared by the birth mother at age 7 [n = 217 siblings in 2013] and additional siblings in both birth and adoptive family homes [n = 881 siblings in 2016]). Data are available in a national repository within the Environmental influences on Child Health Outcomes (ECHO) study and have been integrated into analyses with national and international cohorts. Birth and adoptive families were originally enrolled through a systematic recruitment approach that began with efforts to partner with all domestic adoption agencies in specific regions of the United States following the birth of a child. Longitudinal assessments are ongoing and occurred in 9-month intervals until the adoptees turned 3 years of age, and in 1- to 2-year intervals thereafter to age 21. Data collection includes child temperament, cognition, behavior, and physical health; birth and adoptive parent personality, mental and physical health, context, parenting, and marital relations; the prenatal environment; genetic, hormonal, and cardiovascular data; and geocoding. A unique aspect of the adoption-sibling design is its ability to detect environmental influences on development and test complex interactions and correlations between genetic, prenatal, and postnatal environmental influences on a range of outcomes. The sample and procedures are described, followed by an overview of multicohort findings and opportunities for integration with other registries.
