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.
Abstract Chromosomal microarray is a first-line genetic test for many individuals with neurodevelopmental disorders and congenital anomalies. A common outcome is identification of a copy number variant of uncertain significance (CNV VUS), frequently prompting referral to a clinical genetics service. In the setting of a CNV VUS finding, clinical geneticists often proceed to whole exome sequencing (WES) to determine whether an alternative molecular diagnosis is present. The aim of this study was to determine whether the diagnostic yield of WES differs in individuals with a chromosomal microarray-detected CNV VUS compared with those without a reportable CNV, and to use this difference to estimate the proportion of CNV VUS that are likely to be disease-causing. Individuals who underwent WES at Genetic Health Western Australia (January-December 2022) were included. Phenotype and results were collected from retrospective medical record review. Results found that 32/177 (18%) individuals who underwent WES had an abnormal finding on microarray. WES identified causative variants in 27% overall, with a lower diagnostic yield in those with CNV VUS than those without (11% vs. 30%, p = .023). No diagnoses were made on WES for the 13 patients who had CNV VUS duplications ( p = .020), nor for the 16 individuals with CNV VUS 0.6Mb or larger ( p = .006). It was concluded that individuals with a CNV VUS had a significantly lower diagnostic yield from WES, suggesting that many reportable CNV VUS identified by chromosomal microarray are themselves responsible for the presenting phenotype. Based on the observed difference in diagnostic yield, approximately half of CNV VUS may represent the underlying molecular diagnosis.
Abstract Multiple birth fathers remain largely invisible in perinatal research, policy and practice, despite facing distinctive practical, emotional and financial challenges. This study explores the early parenting experiences of multiple birth fathers in the United Kingdom using qualitative survey data from 107 participants, analysed using thematic analysis. Drawing on a social capital framework, it examines how access to structural, relational and cognitive resources shapes fathers’ wellbeing. Four themes were identified: the complexities of early multiple birth fatherhood, fathers’ mental health, the visibility of their needs, and experiences of support. Fathers described the intensity of raising multiples as ‘doubly hard’, characterized by exhaustion, financial strain, and ‘survival mode’ in the first year. Many reported significant mental health challenges, including stress, guilt, and feelings of being ‘stretched to breaking point’, yet often did not seek support or found available services generic and unhelpful. Experiences of support were inconsistent: while some benefited from flexible employers or strong social networks, others reported minimal professional engagement and perceived services as primarily mother–focused. Peer support from other multiple birth parents was valued but not always accessible. Access to structural resources such as paternity leave, financial support and tailored services was limited, while relational and cognitive resources, including shared understanding from professionals and peers, were uneven. Although UK-based, these findings reflect wider international gaps in father-inclusive perinatal care. Greater recognition of multiple birth fathers, alongside tailored mental health support and multiples-specific services, is needed to improve outcomes for families with multiples.
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 .
