A high prevalence of asthma has been documented among the inhabitants of Tristan da Cunha, an isolated island in the South Atlantic. The population derives from just 28 founders. We performed lung function testing, including methacholine inhalation challenge, allergen skin prick testing, and collected DNA from essentially all of the current island population (269 individuals), and genotyped a panel of 43 single-nucleotide polymorphisms (SNPs) reported as associated with asthma and atopy. We carried out a mixed-model association analysis using the known pedigree. There were 96 individuals diagnosed as asthmatic (36%), and heritability estimates were similar to those from nonisolated population samples (multifactorial threshold model, h2 = 48%). The first component from a genetic principal components analysis using the entire SNP panel was nonlinearly associated with asthma, with the maximum risk to those intermediate to reference (Human Genome Diversity Project) European and African samples means. The single most strongly associated SNP was rs2786098 (p = 5.5 × 10−5), known to regulate the gene DENND1B. This explained approximately one-third of the trait heritability, with an allelic odds ratio for the A allele of 2.6. Among A/A carriers, 10 out of 12 individuals were asthmatic. The rs2786098*A variant was initially reported to decrease the risk of childhood (atopic) asthma in European but slightly increase the risk in African-descended populations, and does significantly alter Th2 cell function. Despite an absence of overall association with this variant in recent asthma genome wide association studies meta-analyses, an effect may exist on the particular genetic background of the Tristan da Cunha population.

Disordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994–1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N = 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling, OR = 0.93 [0.87, 0.99], p = .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG, OR = 1.54 [1.07, 2.21], p = .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.

Genetically informative research designs are becoming increasingly popular as a way to strengthen causal inference with their ability to control for genetic and shared environmental confounding. Co-twin control (CTC) models, a special case of these designs using twin samples, decompose the overall effect of exposure on outcome into a within- and between-twin-pair term. Ideally, the within-twin-pair term would serve as an estimate of the exposure effect controlling for genetic and shared environmental factors, but it is often confounded by factors not shared within a twin-pair. Previous simulation work has shown that if twins are less similar on an unmeasured confounder than they are on an exposure, the within-twin-pair estimate will be a biased estimate of the exposure effect, even more biased than the individual, unpaired estimate. The current study uses simulation and analytical derivations to show that while incorporating a covariate related to the nonshared confounder in CTC models always reduces bias in the within-pair estimate, it will be less biased than the individual estimate only in a narrow set of circumstances. The best case for bias reduction in the within-pair estimate occurs when the within-twin-pair correlation in exposure is less than the correlation in the confounder and the twin-pair correlation in the covariate is high. Additionally, the form of covariate inclusion is compared between adjustment for only one’s own covariate value and adjustment for the deviation of one’s own value from the covariate twin-pair mean. Results show that adjusting for the deviation from the twin-pair mean results in equal or reduced bias.

To improve global human capital, an understanding of the interplay of endowment across the full range of socioeconomic status (SES) is needed. Relevant data, however, are absent in the nations with the most abject poverty (Tucker-Drob & Bates, 2016), where the lowest heritability and strong effects of SES are predicted. Here we report the first study of biopsychosocial gene–environment interaction in extreme poverty. In a sub-Saharan sample of early teenage twins (N = 3192), we observed substantial (~30–40%) genetic influence on cognitive abilities. Surprisingly, shared environmental influences were similar to those found in adolescents growing in Western affluent countries (25–28%). G × SES moderation was estimated at aˋ = .06 (p = .355). Family chaos did not moderate genetic effects but did moderate shared environment influence. Heritability of cognitive abilities in extreme poverty appears comparable to Western data. Reduced family chaos may be a modifiable factor promoting cognitive development.

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983–1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene–environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

Low socioeconomic status (SES) has been established as a risk factor for poor mental health; however, the relationship between SES and mental health problems can be confounded by genetic and environmental factors in standard regression analyses and observational studies of unrelated individuals. In this study, we used a within-pair twin design to control for unmeasured genetic and environmental confounders in investigating the association between SES and psychological distress. We also employed within–between pair regression analysis to assess whether the association was consistent with causality. SES was measured using the Index of Relative Socio-economic Disadvantage (IRSD), income and the Australian Socioeconomic Index 2006 (AUSEI06); psychological distress was measured using the Kessler 6 Psychological Distress Scale (K6). Data were obtained from Twins Research Australia’s Health and Lifestyle Questionnaire (2014–2017), providing a maximum sample size of 1395 pairs. Twins with higher AUSEI06 scores had significantly lower K6 scores than their co-twins after controlling for shared genetic and environmental traits (βW [within-pair regression coefficient] = −0.012 units, p = .006). Twins with higher income had significantly lower K6 scores than their co-twins after controlling for familial confounders (βW = −0.182 units, p = .002). There was no evidence of an association between the IRSD and K6 scores within pairs (βW, p = .6). Using a twin design to eliminate the effect of potential confounders, these findings further support the association between low SES and poor mental health, reinforcing the need to address social determinants of poor mental health, in addition to interventions targeted to individuals.

Due to the high rate of complications, special medical care must be provided especially for monozygotic twin pregnancies, which are characterized as having 2.5 times higher mortality of fetuses. In recent years, examination of cell-free DNA (cfDNA) circulating in maternal plasma has become a useful noninvasive method of prenatal diagnosis. However, fetal DNA constitutes only 3–20% of plasma cfDNA during pregnancy. Short tandem repeats (STRs) are routinely used in forensic examination of DNA mixtures and are able to identify 5% minority components. Haplotypes of deletion/insertion polymorphisms and STRs (DIP–STRs) are able to detect even 0.1% minority components of DNA mixtures. Thus, STRs and DIP–STRs seem to be a perfect tool for detection of fetal alleles in DNA isolated from maternal plasma. Here, we present a novel noninvasive prenatal diagnosis technique of determination of pregnancy zygosity based on examination of feto-maternal microchimerism of plasma cfDNA with the use of STRs and DIP–STRs. Our preliminary results based on 22 STR loci showed 67% sensitivity, 100% specificity and 82% accuracy for prenatal detection of twin dizygosity. The corresponding values for seven DIP–STRs were 13%, 100% and 54%, respectively. Owing to assay performance, low DNA input requirements, low costs (below 10 USD per patient) and simplicity of analysis, genotyping of STR/DIP–STR markers in maternal plasma cfDNA may become a useful supplementary test for noninvasive prenatal diagnosis of twin zygosity in cases when chorionicity and zygosity cannot be reliably determined by ultrasound examination and prognostic value may be provided by a DNA test determining pregnancy zygosity.

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.