Brazilian Twin Studies: A Scoping Review.

The current study was motivated by an interest in deepening understanding of Brazilian twin research, which is underrepresented internationally, in an effort to rectify this situation. Our aim was threefold: (1) to carry out a comprehensive investigation of Brazilian research on twins according to the area of knowledge; (2) to evaluate the representation of research in the field of psychology in comparison with other areas; (3) to evaluate characteristics of the research that may have contributed to its exclusion from the comprehensive meta-analysis of 50 years of twin research. A scoping review was performed according to PRISMA guidelines. Titles and abstracts were searched up to 2022 in six databases: CAPES, BDLTD, PePSIC, PubMed, Google Scholar, and SciELO, using selected keywords both in Portuguese and in English (e.g., 'twins' and 'Brazil'; 'twinning' and 'Brazil'; 'gemelaridade' [twinning], and 'gêmeos' [twins]). Three hundred and forty publications were included in the review. Approximately half (53.8‰) used the classic twin design to investigate the heritability of several traits, and the other half (46.2%) used other research designs. The scoping review showed that the number of publications doubled approximately every 10 years. Most publications were from the health area, with medicine accounting for approximately half of the studies, followed by psychology, odontology, and biology. We found that the interest in studying twins among Brazilian scientists is increasing over the years and there are reasons to be enthusiastic about the potential impact of this trend in the global scenario.

From the Library of the Late Irving I. Gottesman: Memories and Treasures/Twin Research Reviews: Twin Study of Callous-Unemotional Traits; Depressive Symptoms in Prospective Chinese Twin Mothers; Twins With Sagittal Suture Craniosynostosis; Creative Expressiveness and Educational Achievement/Media Reports: Male-Female Twin Holocaust Survivors; Nontuplets Born in Mali; Indian Twins Marry Same Man; Twins Born From Longest-Frozen Embryos; Infant Twin Abduction; Twins Born in Different Years.

The experience of going through the personal library of our late esteemed twin research colleague, Dr Irving I. Gottesman, is described. I came away with fond memories and unexpected treasures. This essay is followed by brief reviews of timely research on factors affecting callous-unemotional traits, depressive symptoms in prospective Chinese twin mothers, twins with sagittal suture craniosynostosis, and creative expressiveness and educational achievement. Media reports on informative topics of interest to researchers and the general public include male-female twin Holocaust survivors, nontuplets born in Mali, Indian twins who married the same man, twins born from the longest frozen embryos, an infant twin abduction and twins born in different years.

Gene Discovery Using Twins.

One of Nick's key early achievements at QIMR was to establish a twin study on melanoma risk factors. The Brisbane Twin Nevus Study (BTNS) had an initial focus on nevus (mole) count in adolescents but, reflecting Nick's broad interests, expanded in scope enormously over the decades. In the skin cancer arena, BTNS was essential to genetic discoveries in melanoma, eye color and pigmentation. Later studies amassed data on thousands of phenotypes, ranging from molecular phenotypes such as gene expression to studies where gene mapping findings in adolescents turned out to have translational potential in late-onset diseases. Nick's twin data have formed the basis for an enormous range of discoveries, with Nick and his colleagues continuing to capitalize on these data.

Statistical Power and the Classical Twin Design.

Dr Nick Martin has made enormous contributions to the field of behavior genetics over the past 50 years. Of his many seminal papers that have had a profound impact, we focus on his early work on the power of twin studies. He was among the first to recognize the importance of sample size calculation before conducting a study to ensure sufficient power to detect the effects of interest. The elegant approach he developed, based on the noncentral chi-squared distribution, has been adopted by subsequent researchers for other genetic study designs, and today remains a standard tool for power calculations in structural equation modeling and other areas of statistical analysis. The present brief article discusses the main aspects of his seminal paper, and how it led to subsequent developments, by him and others, as the field of behavior genetics evolved into the present era.

Birmingham and Beyond.

Nick Martin was a doctoral student of mine at the University of Birmingham in the mid 1970s. In this review, I discuss two of Nick's earliest and most seminal contributions to the field of behavior genetics. First, Martin and Eaves' (1977) extension of the model-fitting approach to multivariate data, which laid the theoretical groundwork for a generation of multivariate behavior genetic studies. Second, the Martin et al.'s (1978) manuscript on the power of the classical twin design, which showed that thousands of twin pairs would be required in order to reliably estimate components of variance, and has served as impetus for the formation of large-scale twin registries across the world. I discuss these contributions against the historical backdrop of a time when we and others were struggling with the challenge of figuring out how to incorporate gene-by-environment interaction, gene-environment correlation, mate selection and cultural transmission into more complex genetic models of human behavior.

Want to Work on Asthma Genetics?

Twins, data and emails. Some of the words that first come to mind when I think of Nick. Lots of twins. With lots of data. And short single-finger-typed emails. And great wine. Well, it works, there is no doubt. That's how I ended up in Australia, working on asthma genetics.

The Genetics of Reading and Language.

Recounts how our collaboration with Nick Martin was shaped over two decades, leading to the first studies of predictions from the 'Dual Route Cascaded' computational model of reading in twins, and extending into the molecular work, first linkage, fine mapping of genes identified in pedigree studies, into now the genomewide association study era and the first polygenic risk scores for reading and their potential in early clarifying causality and validating interventions, as well as for future global collaborations in improving these predictors and identifying causal variants. We highlight Nick's warm, future-focused optimism, support and inclusive approach without which none of this would have been possible. The circle of Nick asking, over half a century ago, 'What genes do you think make some kids get better grades?' has built a diverse scientific legacy involving thousands of papers and collaborations. The (heritable) traits of curiosity, boldness, warmth, interest in societally important questions, openness to new methods, ambition and collaborative skill to bring into being the infrastructure and samples needed for this research are rare, and we are grateful.

Nicholas (Nick) G. Martin and the Extended Twin Model.

The extended twin model is a unique design in the genetic epidemiology toolbox that allows to simultaneously estimate multiple causes of variation such as genetic and cultural transmission, genotype-environment covariance and assortative mating, among others. Nick Martin has played a key role in the conception of the model, the collection of substantially large data sets to test the model, the application of the model to a range of phenotypes, the publication of the results including cross-cultural comparisons, the evaluation of bias and power of the design and the further elaborations of the model, such as the children-of-twins design.

The Genetics of Endometriosis.

Mapping genetic risk factors for endometriosis continues from early studies on women's health initiated by Nick Martin and Susan Treloar. Their initial recruitment of endometriosis cases and family members received a major boost and became a flagship project within the Cooperative Research Centre (CRC) for the Discovery of Common Human Disease. We extended the study through a formal collaboration with Professor Stephen Kennedy and his group in Oxford. Our first joint scientific meeting was held in Brisbane and was sadly memorable as the day the planes were flown into the Twin Towers in New York. Our initial collaboration expanded into the International Endometriosis Genetics Consortium (IEGC). The IEGC now has 15 groups around the world, and the most recent meta-analysis will be published this year.

It's in the Bloody Genes!

Blood cell concentrations for most cell types are highly heritable. Data from Nick Martin's twin registry provided much of the data for the early heritability and linkage studies of blood cell related traits and have contributed significantly to more recent genomewide association studies that have successfully identified individual genetic loci.

Musings on Visscher et al. (2006).

The classical twin design relies on a number of strong number of assumptions in order to yield unbiased estimates of heritability. This includes the equal environments assumption - that monozygotic and dizygotic twins experience similar degrees of environmental similarity - an assumption that is likely to be violated in practice for many traits of interest. An alternative method of estimating heritability that does not suffer from many of these limitations is to model trait similarity between sibling pairs as a function of their empirical genome-wide identity by descent sharing, estimated from genetic markers. In this review, I recount the story behind Nick Martin's and my development of this method, our first attempts at applying it in a human population and more recent studies using the original and related methods to estimate trait heritability.

A Brief History of the Collaboration between Dr Nathan Gillespie and Professor Nick Martin Including Personal Reflections.

This article describes Dr Nathan Gillespie's PhD training and supervision under Professor Nick Martin and their ongoing collaborations. Drs Gillespie and Martin have collaborated on numerous biometrical genetic analyses applied to cross-sectional and longitudinal twin data, combined molecular and phenotypic modeling, as well as genomewide meta-analyses of psychoactive substance use and misuse. Dr Gillespie remains an active collaborator with Professor Martin, including ongoing data collection, analysis and publications related to the Brisbane Longitudinal Twin Study.

Cohorts.

Cohort studies are essential for conducting large studies of multiple exposures and outcomes in humans. Recently, the ability to combine data from multiple cohorts in, for example, meta-analyses, and the willingness in the genetics community to collaborate to enable replication studies has led to many new insights into the genetic and environmental determinants of human health and behaviors. The contribution of Professor Nicholas Martin to the development of cohort studies, particularly of twin and twin-family studies, over a period of several decades is reviewed. He has contributed to the development and use of both Australian and international resources. The contributions of Australian twin studies to genomewide association projects are multiple, and across multiple domains, from biomarkers, lifestyle and behavior to disorders and disease.

The Rare Sides of Twin Research: Important to Remember/Twin Research Reviews: Representation of Self-Image; Twins With Kleine-Levin Syndrome; Heteropaternal Lemur Twins; Risk of Dental Caries/In the Media: High-Society Models; 'Winkelevii' Super Bowl Twins; Multiple Birth × Three; Twin Sister Surrogate; A Presidential Twin?

This article explores some rare sides of twin research. The focus of this article is the sad plight of the Dionne quintuplets, born in Canada in 1934. However, several other studies belong in this category, such as Dr Josef Mengele's horrifying twin research conducted at the Auschwitz concentration camp, Dr John Money's misguided attempt to turn an accidentally castrated male twin into a female, Russian scientists' cruel medical study of conjoined female twins and Dr Peter Neubauer's secret project that tracked the development of separated twins. Reviews of current twin research span twins' representation of self-image, twins with Kleine-Levin Syndrome, heteropaternal twinning in lemurs and factors affecting risk of dental caries. Media coverage includes a pair of high-society models, a book about the 'Winkelevii' twins, Super Bowl twin teammates, a family with three sets of fraternal twins, a twin sister surrogate and a near presidential twin.

The Louisville Twin Study: Past, Present and Future.

The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The LTS is unique because of the extensive longitudinal face-to-face assessments, the frequency of data collection, the inclusion of data on additional family members (i.e., parents, siblings, grandparents; and later, twins' own spouses and children), and the variety of data collection methods used. Data preservation efforts began in 2008 and are largely complete, although efforts are ongoing to obtain funding to convert the electronic data to a newer format. A pilot study was completed in the summer of 2018 to bring the twins, who are now middle-aged, back for testing. A grant is currently under review to extend the pilot study to include all former participants who are now ≥40 years of age. Opportunities for collaboration are welcome.

The Chinese National Twin Registry: a 'gold mine' for scientific research.

The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same-sex dizygotic and opposite-sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease-concordant or disease-discordant twin pairs or from twin pairs reared apart. More than 8000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs. In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene-environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.

Aspects of the History of Twin Research: Statistical Congresses in the 19th Century and Hellin's Law.

In the 19th century, a series of international statistical congresses began that were important for population studies, including twin research. The introduction of common rules for the national demographic registers enabled scientists to contribute to the genesis of statistical research. The congress in St. Petersburg in 1872, in particular, focused on the movements of the population, and how they should be registered. Among the facts to be recorded were in multiple births, the sex and number of children born alive or still-born, whether legitimate or illegitimate, and the age of the mother at the date of the births. During the history of twin research, Hellin's law has played a central role because it is an approximately correct association between the rates of multiple maternities. It has been mathematically proven that Hellin's law does not hold as a general rule. Analyses show divergences from the law that are difficult to explain and/or eliminate. Varying improvements of this law have been proposed. The majority of all studies of Hellin's law are based on empirical rates of multiple maternities, ignoring random errors. Such studies can never confirm the law, but only identify errors with respect to Hellin's law that are too large to be characterized as random. It is of particular interest to note and explain why the rates of higher multiple maternities are sometimes too high or too low when Hellin's law is used as a benchmark. Studies have shown that there were investigators before Hellin who have contributed substantially to Hellin's law. In this article, we re-examine some old data sets and contributions in which Hellin's law has been evaluated and also analyze recent data.

Oliver Sacks: Our Correspondence About Twins/Twin Research: Vanishing Twins Syndrome; Discordant Sex in MZ Twins; Pregnancy Outcomes in IVF and ICSI Conceived Twins/Print and Media: Superfetated Twins; Twins Discordant for Smoking; Twins in Fashion; Yale University Twin Hockey Players; Conjoined Twin-Visiting Professor.

The late neurologist and author, Oliver Sacks, published an insightful 1986 review of Marjorie Wallace's book, The Silent Twins, in the New York Times. Taking exception to his assertion about Sir Francis Galton, I wrote a letter to the Times' editor. The letter was unpublished, but it brought a wonderful response from Sacks himself that is reproduced and examined. Next, brief reviews of twin research concerning the vanishing twin syndrome (VTS), discordant sex in a monozygotic (MZ) twin pair, and multiple pregnancy outcomes from assisted reproductive technology (ART) are presented. This section is followed by popular coverage of superfetated twins, smoking-discordant co-twins, twins in fashion, Yale University twin hockey players, and a visiting professor who was a conjoined twin.