Twin Research and Human Genetics最新文献

{"title":"Data Resource Profile: The Finnish TwinRegistry Project.","authors":"Stephanie Zellers, Sarah Niemi de Paiva, Mikko Olkkonen, Hannu Karhunen, Terhi Maczulskij, Annina Ropponen, Jaakko Kaprio, Antti Latvala","doi":"10.1017/thg.2025.10025","DOIUrl":"https://doi.org/10.1017/thg.2025.10025","url":null,"abstract":"<p><p>The Older Finnish Twin Cohort was established 50 years ago and includes twins born in Finland before 1958. Members of the cohort have responded to detailed questionnaires about their health, habits, and lifestyle up to four times, in 1975, 1981, 1991, and 2011. In 2019, the Finnish Parliament approved the Act on the Secondary Use of Health and Social Data, which enables wider use of data from national social and healthcare registers as well as various patient systems and social services. This data resource article describes the linkage of the Older Finnish Twin Cohort to numerous social and healthcare registers, alongside linked data from their families and the broader Finnish population born in 1945-1957, which serves as a reference population for generalizability and other analyses.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is the General Factor of Personality an Entity? Testing Reflective, Formative, and Mixed Models of Polygenic Score Influence Using the English Longitudinal Study of Aging.","authors":"Michael A Woodley, Mateo Peñaherrera-Aguirre, Matthew A Sarraf","doi":"10.1017/thg.2025.10024","DOIUrl":"https://doi.org/10.1017/thg.2025.10024","url":null,"abstract":"<p><p>Leveraging a unique dataset (the English Longitudinal Study of Aging) containing polygenic scores (PGSs) - estimated using meta-analytically-derived single nucleotide polymorphisms (SNPs) for the Big Five (BF) - the General Factor of Personality's (GFP) existence as a veritable psychometric entity was investigated. Exploratory tests involving a subsample of 200 participants revealed that while the BF PGSs were adequate for factor analysis, parallel analysis suggested the presence of zero factors, indicating no \"genetic GFP\" among these PGSs, but did indicate the presence of a robust latent GFP among the phenotypic BF. Confirmatory factor analysis involving an independent sample of 4,533 participants was used to compete three models: full mediation by the GFP of PGS effects on the BF (common pathway or <i>reflective</i>); full mediation by the BF of PGS effects on the GFP (independent pathways or <i>formative</i>); and a mixed model. All models exhibited good fit, with the reflective model having the greatest parsimony. Statistically significant covariances were also observed among the PGSs, potentially consistent with pleiotropy. Even though the reflective model fit best, the common paths were extremely weak (and could be set to zero in most cases), with only the (negatively signed) path from the extraversion PGS to the GFP reaching significance. This finding is (weakly) consistent with the hypothesis that the GFP is a valid entity.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral Genetics and Human Agency: How Selectively Deterministic Theories of Free Will Drive Unwarranted Opposition to Behavioral Genetic Research and Undermine Our Moral and Legal Conventions, Part II.","authors":"Damien Morris","doi":"10.1017/thg.2025.10015","DOIUrl":"https://doi.org/10.1017/thg.2025.10015","url":null,"abstract":"<p><p>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 <i>all</i> 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 <i>comprehensive</i> 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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-15"},"PeriodicalIF":1.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twins in Naturalistic Context: Highlights from the International Society for Human Ethology/Twin Research Reviews: Twins with Feingold Syndrome; Twins' Language Delays; Breastfeeding Twins; Twins with Olmsted Syndrome/In the News: Loss of Texas Twins; A Singular Musical Sensation; Conjoined Twin Deliveries in Myanmar and India; Major League Baseball Pairs.","authors":"Nancy L Segal","doi":"10.1017/thg.2025.10020","DOIUrl":"https://doi.org/10.1017/thg.2025.10020","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upholding Protocol - The Logic of Diagnosis - Tribute to E. M. Nicholls (1927-2011).","authors":"Alan E Stark, Paulo A Otto","doi":"10.1017/thg.2025.10017","DOIUrl":"10.1017/thg.2025.10017","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-2"},"PeriodicalIF":1.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Seven-Gene Signature for the Diagnosis of Parkinson's Disease and Immune Infiltration Analysis.","authors":"Chengqun Wei, Rui Xue, Zhan Gao, Hongyan Zhu, Xiuzhi Xu","doi":"10.1017/thg.2025.10008","DOIUrl":"10.1017/thg.2025.10008","url":null,"abstract":"<p><p>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 <i>CD79B</i>, <i>CD40</i>, <i>CCR9</i>, <i>ADRA2A</i>, <i>SIGLEC1</i>, <i>FLT3LG</i>, and <i>THBD</i>, 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. <i>CD79B</i>, <i>CD40</i>, <i>CCR9</i>, <i>ADRA2A</i>, <i>SIGLEC1</i>, <i>FLT3LG</i>, and <i>THBD</i> were identified as diagnostic markers for PD, and the infiltration of immune cells may contribute to the pathogenesis of the disease.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutual Tissue Microchimerism of Hepatoblastomas in Monozygotic Twins From a Familial Adenomatous Polyposis Family.","authors":"Atsuhiro Arisue, Kiyoshi Yamaguchi, Kiyoko Takane, Yoshiko Asakura, Yasushi Hasegawa, Masaru Mizuno, Hiroyuki Nitta, Kazuyuki Ishida, Takeshi Iwaya, Eigo Shimizu, Seiya Imoto, Satoru Miyano, Yoichi Furukawa, Satoshi S Nishizuka","doi":"10.1017/thg.2025.10019","DOIUrl":"https://doi.org/10.1017/thg.2025.10019","url":null,"abstract":"<p><p>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 <i>APC</i>, Sanger sequencing was applied for the twins, the father, and the siblings of the father. A pathogenic variant of the <i>APC</i> gene was identified in the father as well as the twins. The WES of the HBs in the twins identified somatic mutations, including an <i>NRAS</i> mutation in the tumor of the first infant (C1), and an <i>ACVR2A</i> 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 <i>NRAS</i> mutation was found in multiregional specimens of C1 and those of C2. The <i>ACVR2A</i> 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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Overlooked Legacy: Genetic Contributions of the Childless.","authors":"Vergard F Skirbekk, Bernt Bratsberg, Christian M Page, Dana Kristjansson","doi":"10.1017/thg.2025.25","DOIUrl":"https://doi.org/10.1017/thg.2025.25","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-7"},"PeriodicalIF":1.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Mediation of Cognition by DNA Methylation and Lean Body Mass in Chinese Monozygotic Twins.","authors":"Huihui Li, Tong Wang, Xiaocao Tian, Dongfeng Zhang, Weijing Wang","doi":"10.1017/thg.2025.10014","DOIUrl":"https://doi.org/10.1017/thg.2025.10014","url":null,"abstract":"<p><p>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 <i>PDGFRB</i> and <i>RP11</i> genes (ACME: -0.0972-0.0463, |ACME/ADE|: 10.44%-18.30%) negatively mediated the association between LBM and cognition, while one in the <i>PAX2</i> gene (ACME: 0.3510, |ACME/TE|: 11.84%) positively mediated the association. Besides, the methylation risk score (MRS) of <i>RP11</i> 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 <i>UBXN6</i> and cognition (ACME: -0.0732, |ACME/TE|: 20.78%), while positively mediated the association between the DNAm level of four CpGs within <i>FOXI2</i> and cognition (ACME: 0.2812-0.4496, |ACME/TE|: 18.15%-27.29%). It was found the DNAm in <i>PDGFRB</i>, <i>RP11</i> and <i>PAX2</i> partially mediates the association between LBM and cognition, and the association between DNAm in <i>UBXN6</i> and <i>FOXI2</i> with cognition is also partially mediated by LBM.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twins of Greece: International Symposium on Twins and Twin-Related Events/Twin Research Reviews: Twins' Neonatal Outcomes; Growth Discordance and Growth Restriction; Twins' Romantic Partners and Alcohol Use/Human Interest Stories: The Paget Twins' Extraordinary Lives; Museum Wing Honors the Lost Rockefeller Twin; Remarkable Conjoined Twins in India; Death of an Australian Sports Icon; A Most Unusual Triplet Birth.","authors":"Nancy L Segal","doi":"10.1017/thg.2025.10012","DOIUrl":"https://doi.org/10.1017/thg.2025.10012","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}