Twin Research and Human Genetics最新文献

This article argues that a pervasive but confused theory of free will is driving unwarranted resistance to behavioral genetic research and undermining the concept of personal responsibility enshrined in our moral and legal conventions. We call this the theory of 'free-will-by-subtraction'. A particularly explicit version of this theory has been propounded by the psychologist Eric Turkheimer, who has proposed that human agency can be scientifically quantified as the behavioral variation that remains unexplained after known genetic and environmental causes have been accounted for. This theory motivates resistance to research that suggests genetic differences substantially account for differences in human behavior because that is seen to reduce the scope of human freedom. In academic philosophy, free-will-by-subtraction theory corresponds to a position called 'libertarian incompatibilism', which holds that human beings are not responsible for behavior that has antecedent causes yet maintains that free will nonetheless exists because some fraction of human behavioral variation is self-caused. However, this position is rejected by most professional philosophers. We argue that libertarian incompatibilism is inconsistent with a secular materialist outlook in which all human behavior is understood to have antecedent causes whether those causes are known to science or not - an outlook Turkheimer shares. We show that Turkheimer sustains this contradiction by adopting an untenable position we call 'epistemic libertarianism', which holds that antecedent causes of our behavior only infringe on our freedom if we know about them. By contrast, the overwhelming majority of secular materialist philosophers support a position called 'compatibilism', which maintains that free will is compatible with the comprehensive causation of human behavior. We show that compatibilism neutralizes the threat that genetic explanation poses to human agency and rescues a generous conception of personal responsibility that aligns with our moral intuitions.

Twin highlights from the 2025 summer meeting of the International Society for Human Ethology are reviewed. The value of observing twins in naturalistic and semi-naturalistic settings is revealed. Research reports involving twins with Feingold syndrome, twins with language delays, breastfeeding of twins, and twins with Olmsted syndrome are reviewed. The final section of this article covers timely and informative news of twins in the media. Topics include the loss of young Texas twins in the devasting July 4th flood, a sensational - and singular - musical twin performer, conjoined twin deliveries in Myanmar and India, and two pairs of twins headed to major league baseball teams.

Max Nicholls had an almost unique experience as a medical practitioner, researcher and teacher of medical genetics. An earlier paper described his contribution to the etiology of neurofibromatosis. This was followed by Nicholls' own experience as lecturer in the Faculty of Medicine, University of New South Wales, Australia. This note draws attention to his research in immunology. For example, he was instrumental in the study of the buffy coat leuko-agglutination (BCLA) test, a sensitive assay for cell-mediated immunity that he introduced to detect conditions (including cancer) in preclinical stages.

The objective was to identify the predictive markers and develop a diagnostic model with predictive markers for Parkinson's disease (PD) and investigate the roles of immune cells in the disease pathology. Microarray datasets of PD and control samples were obtained from the Gene Expression Omnibus (GEO) database. We then performed a comprehensive analysis of differentially expressed genes (DEGs), functional enrichment, and protein-protein interactions to pinpoint a set of promising candidate genes. To establish a diagnosis model for PD, we utilized machine learning algorithms and evaluated the corresponding diagnostic performance using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). Additionally, the differential abundance of immune cell subsets between PD and control samples was evaluated using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. A total of 264 DEGs were identified in GSE72267. The PPI network ultimately identified 30 hub genes for model construction. Seven genes, namely CD79B, CD40, CCR9, ADRA2A, SIGLEC1, FLT3LG, and THBD, were identified as diagnostic markers for PD, with an AUC of 0.870. This seven-gene signature model was subsequently validated in an independent cohort (GSE22491), demonstrating an AUC of 0.825. Ultimately, the infiltration of 28 immune cells showed that activated B cells, natural killer T cells, and regulatory T cells may contribute to the occurrence and progression of PD. We also found complex associations between these genes and immune cells. CD79B, CD40, CCR9, ADRA2A, SIGLEC1, FLT3LG, and THBD were identified as diagnostic markers for PD, and the infiltration of immune cells may contribute to the pathogenesis of the disease.

Patients with familial adenomatous polyposis (FAP) have increased risk of hepatoblastoma (HB). We report monozygotic twins with HB in a FAP family. To explore genetic alterations in the HBs of the twins, we carried out whole exome sequencing (WES), RNA-seq, and immunohistochemical analyses of the tumors. Additional multiregional digital PCR was performed to profile clonality of each tumor. To determine a pathogenic germline variant in APC, Sanger sequencing was applied for the twins, the father, and the siblings of the father. A pathogenic variant of the APC gene was identified in the father as well as the twins. The WES of the HBs in the twins identified somatic mutations, including an NRAS mutation in the tumor of the first infant (C1), and an ACVR2A mutation in the tumor of the second infant (C2). No somatic mutations were identified in the genes associated with the Wnt signaling pathway. However, accumulation of β-catenin was found in the C1 and C2 tumors by immunohistochemical staining, suggesting activation of the Wnt signaling pathway. Digital PCR analysis revealed that the NRAS mutation was found in multiregional specimens of C1 and those of C2. The ACVR2A mutation was found in multiregional specimens of C2, whereas the mutation was also identified in those of C1. The existence of a shared somatic mutation may suggest that microchimerism took place in the development of HBs through the utero-placental circulatory system. Importantly, the initiation of tumorigenesis is thought to occur during the fetal period after organ development of the liver.

Childless individuals have historically faced stigma with assumptions that they lack an interest in future generations because they do not directly contribute to genetic lineage. Individuals share approximately half of their genes with siblings, 12.5% with first cousins, and 6.25% with first cousins' children. Norwegian census data (2005-2023), reflecting similar trends to the US, UK, and other European countries, indicates a moderate difference in the number of siblings (Parents: 2.03 [women and men]; Childless: 1.88 [women], 1.94 [men]) and nieces/nephews (Parents: 3.99 [women], 4.03 [men]; Childless: 3.32 [women], 3.42 [men]) for 514,777 women and 532,834 men, respectively. By linking four generations through grandmothers, both childless and childbearing women had a slightly higher number of biological extended family members (Parents: 9.63 cousins with 15.79 children; Childless: 8.66 cousins with 12.22 children). Linking four generations for men, numbers were similar: Parents: 9.68 cousins with 15.91 children, Childless: 8.83 cousins with 12.44 children. Based on the average number of children who are parents, the childless have an average genetic fitness that is 49% of that for parents for the next generation. Both parents and childless individuals have a stake in future generations through their biological extended family.

This study explores whether DNA methylation (DNAm) mediates the association between lean body mass (LBM) and cognition, as well as whether LBM mediates the association between DNAm and cognition. Based on the data of 59 monozygotic twin pairs, mediation analyses were performed using causal inference test method and mediation analyses. Average causal mediation effect (ACME), average direct effect (ADE), and total effect (TE) were calculated. Among the CpGs associated with LBM, five located within PDGFRB and RP11 genes (ACME: -0.0972-0.0463, |ACME/ADE|: 10.44%-18.30%) negatively mediated the association between LBM and cognition, while one in the PAX2 gene (ACME: 0.3510, |ACME/TE|: 11.84%) positively mediated the association. Besides, the methylation risk score (MRS) of RP11 gene (ACME: -0.0517, |ACME/ADE|: 10.64%) and MRS of all CpGs (ACME: -0.0511, |ACME/ADE|: 10.53%) negatively mediated the association of LBM with cognition. For another, LBM negatively mediated the association between the DNAm level of one CpG within UBXN6 and cognition (ACME: -0.0732, |ACME/TE|: 20.78%), while positively mediated the association between the DNAm level of four CpGs within FOXI2 and cognition (ACME: 0.2812-0.4496, |ACME/TE|: 18.15%-27.29%). It was found the DNAm in PDGFRB, RP11 and PAX2 partially mediates the association between LBM and cognition, and the association between DNAm in UBXN6 and FOXI2 with cognition is also partially mediated by LBM.

Highlights from the International Symposium on Twins, held at the University of Crete on May 23-24, 2025, are summarized. The symposium, organized by Dr Maria Markodimitraki, Professor in the Department of Preschool Education at the University of Crete, attracted scholars and practitioners from Greece and around the world. Meetings with a pair of reunited monozygotic female twins, and a female twin in search of her sister, also from Greece, are described. This review is followed by summaries of twin research on neonatal outcomes, growth discordance and restriction, and romantic partners and alcohol use. Human interest stories include a book documenting the extraordinary lives of identical twins Celia and Mamaine Paget, a museum wing honoring the lost Rockefeller twin, a remarkable conjoined twinning case in India, the death of an Australian sports icon, and a most unusual triplet birth.

Depression, a leading cause of global disability, arises from a multifaceted combination of genetic and environmental components. This study explores the relationship between major depressive disorder (MDD) polygenic scores (PGS), characteristics and symptoms of depression, and community-shared socioeconomic factors derived from postal code data in a cohort of 12,646 individuals from the Australian Genetics of Depression Study (AGDS). Our findings reveal that people living in areas with relatively higher socioeconomic advantages and education/occupation scores are more likely to report experiencing fewer depressive symptoms during their worst depressive period, as well as fewer number of lifetime episodes. Additionally, participants who reported depression onset later in life tend to currently reside in wealthier areas. Interestingly, no significant interaction between genetic and socioeconomic factors was observed, suggesting their independent contribution to depression outcomes. This research underscores the importance of integrating socioeconomic factors into psychiatric evaluation and care, and points to the critical role of public policy in addressing mental health disparities driven by socioeconomic factors. Future research should aim to further elucidate the causal relationships within these associations and explore the potential for integrated genetic and socioeconomic approaches in mental health interventions.

Sense of humor is a universal human trait, enjoyed daily across cultures. However, little is known about the factors that shape individual differences in humor, particularly what contributes to developing a great sense of humor. While previous studies have identified a significant genetic component for various humor attributes, such as humor appreciation and humor styles, no study has looked at the heritability of humor production ability. This study is the first to assess the genetic and environmental influences on humor production ability using a twin study design. Participants included 448 pairs of monozygotic twins and 196 pairs of dizygotic twins (median age 66 years, mostly female) from the Twins UK registry. Twins self-assessed their humor ability, rated the funniness of their co-twin, and completed an objective humor production task by composing funny captions for captionless cartoons. Additionally, they completed a short cognitive ability test and reported their overall health. Findings revealed that self-rated humor ability was influenced by both additive genetic and nonshared environmental factors. In contrast, objective humor production showed no evidence of additive genetic effects. Instead, all individual differences were shaped by shared and nonshared environmental influences, though a small genetic effect cannot be ruled out. These results suggest that humor production may be more complex and difficult to assess than other cognitive abilities. The study also presents intriguing implications for the evolutionary basis of humor.