Abstract The main feature of this essay concerns a dizygotic triplet set born to a gay male couple. In vitro fertilization (IVF), using egg donation and surrogacy, is becoming a more common method of choice for same-sex male couples wishing to have families. This story is followed by a tribute to a late colleague, Dr Alec Roy. The next section presents twin research reviews of dog ownership, twinning rates in Awassi ewes, monozygotic male twins with mitochondrial encephalomyopathy, and a novel twin study of meditation. Several human-interest items capture other informative aspects of twinship. They include twins with unrelated biological parents, twins born in different years, a valedictorian−salutatorian pair; highlights from the Annual Twins Days Festival, an FBI identical twin identification dilemma, and a pair of identical twin doctors.
Prospective cohorts show that a postinfective fatigue syndrome (PIFS) meeting criteria for chronic fatigue syndrome (CFS) develops in roughly 1 in 10 people after diverse acute infections, independent of the triggering pathogen. Whether constitutional liability to affective disorders contributes has been debated but not tested at the level of measured genetic risk. Using the Dubbo Infection Outcomes Study (DIOS), we tested whether polygenic liability to major depressive disorder (MDD), and to CFS, predicts PIFS. Participants with serologically confirmed infection were followed at regular intervals before a physician-and psychiatrist-assessed diagnosis of PIFS at 6 months. Polygenic scores for MDD and CFS were derived from external GWAS using SBayesRC and tested as predictors of PIFS diagnosis using logistic regression, adjusted for sex, age, and ten principal components. Effect modification by sex was examined as an exploratory analysis. Of 464 participants (89 cases, 375 controls), neither MDD-PGS (adjusted OR = 0.99, 95% CI [0.78, 1.26], p = .95) nor CFS-PGS (adjusted OR = 0.97, 95% CI [0.77, 1.23], p = .81) predicted PIFS diagnosis. In exploratory analysis, the MDD-PGS & times; sex interaction was suggestive (Wald p = .06; Firth penalized p = .04), with higher MDD-PGS associated with increased odds of PIFS in women but decreased odds in men. The CFS-PGS & times; sex interaction was nonsignificant. Common-variant polygenic liability to major depression or to chronic fatigue did not predict PIFS diagnosis in this cohort, but a suggestive sex-dependent effect of major depression polygenic risk warrants replication in adequately powered cohorts.
Abstract Dizygotic twinning (DZT) is an important marker of female fertility. The Twinning Genetics Consortium (TGC) recently reported the largest genomewide association meta-analysis (GWAMA) of DZT, identifying six genomewide significant loci and a seventh supported by functional evidence, in 8265 mothers of spontaneous DZ twins (MoDZTs) and 264,567 European-ancestry controls. To identify additional loci, we continued recruitment of MoDZTs in Australia and New Zealand (ANZ). Here, we report a GWAS of a new ANZ2026 sample (1598 MoDZTs and 5317 controls) and a GWAMA combining this sample with the previously reported ANZ2023 dataset. A new locus near CLYBL on chromosome 13 was tentatively identified. Because CLYBL is associated with vitamin B12 levels linked to fertility, it represents a plausible candidate. However, despite a 51% increase in ANZ cases, only one additional locus emerged, supporting the hypothesis that DZT is an oligogenic rather than highly polygenic trait. Meta-analysis with the TGC2024, the largest existing GWAS of DZT, strengthened signals at several loci, including HLA-G, while weakening others, such as ZFPM1 .
Abstract Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Current pharmacological treatments have limitations, highlighting the need for new therapeutic targets. Using two-sample Mendelian randomization with cis-expression quantitative trait loci from the eQTLGen Consortium (31,684 individuals), we performed genomewide analysis against ADHD genomewide association study summary statistics from European ancestry (20,183 cases; 35,191 controls) and FinnGen R10 (2,788 cases; 405,153 controls). Genetic instruments were selected at p < 5 × 10 −8 with F -statistic > 10 and linkage disequilibrium clumping ( r 2 < .001). Mendelian randomization estimates were derived using inverse-variance weighted, weighted-median, and Mendelian randomization-Egger methods, with leave-one-out sensitivity analysis. Colocalization was performed to distinguish causality from linkage disequilibrium. From 5430 genes with valid instruments, we identified 10 ADHD-associated genes (inverse-variance weighted p < .01, consistent direction across methods): four risk-increasing genes ( RRAGD, DTX2, HMOX1, AGAP3 ) and six protective genes ( NUCKS1, CPSF1, MAU2, CLDN5, CYP4F12, ATP6V1E2 ). MAU2 demonstrated strong colocalization support (posterior probability for hypothesis 4 > .6). Pathway enrichment highlighted mechanistic target of rapamycin signaling as a priority mechanism. Computational in silico drug prioritization nominated candidate compounds (e.g., selenium, ketoconazole) predicted to modulate these targets. This study identifies genetically supported therapeutic targets for ADHD. MAU2 emerged as the most promising causal locus. Rapamycin signaling represents a key mechanistic pathway. Several repositioned candidates (e.g., selenium, ketoconazole) warrant further experimental evaluation as potential leads. These findings provide a hypothesis-generating foundation for drug target prioritization, and require functional confirmation in CNS models and clinical validation before therapeutic relevance can be established.
Abstract Prior literature using twin pairs in the same or different classes found classroom effects accounted for between 8% and 2−3% of the variability in literacy achievement depending on the method, grade, or measure used. The current study examines whether this effect could be greater (or less) than this depending on a child’s levels of inattention and hyperactivity. The sample comprised 758 identical and same-sex fraternal twin pairs from an international longitudinal twin study of early literacy development. The study used scores on word reading, spelling and reading comprehension, and parent ratings on the Disruptive Behaviour Rating Scale (DBRS) for children in kindergarten (aged x overbar x ¯ $\bar x$ = 6.2, s = 0.3), Grade 1 and Grade 2. Contrary to predictions, the results failed to support the prediction, indicating that classroom-level effects are independent of the behavior issues measured in this study.
