Twin Research and Human Genetics最新文献

{"title":"Genetic Contributions to BMI Fluctuation and Its Associations With BMI and Its Trajectories Over Adolescence and Early Adulthood: A 25-Year Follow-Up Longitudinal Study of Finnish Twins.","authors":"Alvaro Obeso, Aline Jelenkovic, Jose Angel Peña, Gabin Drouard, Sari Aaltonen, Jaakko Kaprio, Karri Silventoinen","doi":"10.1017/thg.2025.10030","DOIUrl":"https://doi.org/10.1017/thg.2025.10030","url":null,"abstract":"<p><p>We examined how BMI, BMI trajectories, and BMI fluctuation around these trajectories in adolescence were correlated with BMI trajectories and BMI fluctuation in early adulthood, as well as the genetic basis of these associations. BMI data from Finnish twins (<i>N</i> = 1379, 48% males) were collected at ages 11.5, 14, 17.5, 24, and 37 years. BMI trajectories in adolescence (11.5-17.5 years) and early adulthood (17.5-37 years) were estimated using linear mixed-effect models. BMI fluctuation was calculated as the average squared differences between observed and expected BMI around these trajectories. Genetic twin models and a polygenic risk score for BMI (PRS_BMI) were used to assess genetic contributions to BMI fluctuation and its associations with BMI and BMI trajectories. Adolescent BMI fluctuation was positively correlated with early adulthood BMI trajectories in females, while in males, adolescent BMI trajectories were positively associated with BMI fluctuation in early adulthood. Genetic factors affected BMI fluctuation in both adolescence and early adulthood when estimated using twin modelling and PRS_BMI. Adolescent BMI was positively associated with early adulthood fluctuation in both sexes, with genetic factors playing a role (genetic correlations .08-.29). It was concluded that genetic factors play a significant role in BMI fluctuations in adolescence and early adulthood, with some overlap with the genetics of BMI.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330067","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 III.","authors":"Damien Morris","doi":"10.1017/thg.2025.10016","DOIUrl":"https://doi.org/10.1017/thg.2025.10016","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":"1-16"},"PeriodicalIF":1.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313738","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":"Trends and Factors Associated with Under-5 Excess Mortality among Twins in sub-Saharan Africa: A Study of 156 National Surveys from 42 Countries.","authors":"Adama Ouedraogo, Sophie Le Coeur, Gilles Pison, Abdramane B Soura","doi":"10.1017/thg.2025.10007","DOIUrl":"https://doi.org/10.1017/thg.2025.10007","url":null,"abstract":"<p><p>Twin children are more likely to die than singletons. This is an additional burden in sub-Saharan African (SSA) countries, as child mortality levels are already higher than anywhere else. This article provides estimates of under-5 mortality rates (U5MRs) for twins and singletons in SSA from 1986 to 2016. It describes the geographical variations and changes over time. It also describes the variation of twins' excess mortality according to age from 0 to 5 years. Additionally, it analyzes the factors associated with twins' excess mortality. We used data from 156 national surveys from 42 countries. We estimated U5MRs for twins and single children and built a Cox model to analyze factors associated with excess mortality among twins. Although child mortality has declined on the continent, twins' excess mortality remains very high. U5MRs are, on average, 3 times higher among twins than singletons. The Cox model shows that all other things being equal, the adjusted hazard ratio of under-5 mortality (U5M) is 3.2 (2.9-3.3; <i>p</i> < .001) times higher among twins than singletons. The main factors associated with excess mortality risks among twins are biomedical and nutritional features, such as low birth weight, non-use of cesarean section delivery, and lack of breastfeeding. Health policy makers in SSA should be aware of the vulnerability of twins, and interventions to prevent their early deaths should be considered.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-21"},"PeriodicalIF":1.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281161","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}