Twin Research and Human Genetics最新文献

{"title":"Identification of Mediating Pathways Between Attention Deficit/Hyperactivity Disorder and Coronary Artery Disease and Heart Failure: A Two-Step Multivariable Mendelian Randomization Study.","authors":"Jing Lin, Yiling Zhou, Tian Xie, Jia Zhang, Zekai Chen, Zheng Chang, Yaogang Wang, Harold Snieder, Chris H L Thio, Catharina A Hartman","doi":"10.1017/thg.2025.10037","DOIUrl":"https://doi.org/10.1017/thg.2025.10037","url":null,"abstract":"<p><p>Attention deficit/hyperactivity disorder (ADHD) is associated with an increased risk of cardiovascular diseases (CVDs). However, whether this is a causal relation and how ADHD may predispose to a higher risk of CVD needs to be determined. We aimed to assess the causal association between ADHD and both coronary artery disease (CAD) and heart failure (HF), and to quantify the mediating effects of potential modifiable mediators. We conducted a two-step, two-sample Mendelian randomization (MR) study using SNPs as genetic instruments for exposure and potential mediators. Leveraging summary data on the latest genomewide association studies for ADHD, proposed mediators (i.e., metabolic factors, inflammatory factors, lifestyle behaviors, psychiatric disorders, and educational attainment), CAD and HF, we decomposed the total effect of ADHD on each outcome into direct and indirect effects through multiple mediators. Genetically predicted ADHD was associated with increased odds of CAD (<i>OR</i> 1.13; 95% CI [1.07, 1.19]), with educational attainment (EA) being the largest contributor (32.27% mediation, 95% CI [18.33%, 56.93%]). Body mass index (BMI), type 2 diabetes (T2D), EA, smoking initiation (SI), and depression jointly explained 83.59% (95% CI [63.95%, 101.49%]) of the association. Genetically predicted ADHD was associated with increased odds of HF (<i>OR</i> 1.11; 95% CI [1.05, 1.19]), with SI being the largest contributor (35.87% mediation, 95% CI [13.75%, 100.14%]). BMI, T2D, and SI jointly explained 82.39% (95% CI [45.90%, 131.60%]) of the association. The findings support a causal relationship between ADHD and both CAD and HF. Several modifiable risk factors substantially mediate these associations, suggesting potential targets for interventions aimed at reducing CVD risk in individuals with ADHD.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935269","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":"Human Genetics Society of Australasia Position Statement: Online or Direct-to-Consumer Genomics Testing.","authors":"Julia Mansour, Rebekah McWhirter, Alison McLean, Alison McIvor, Natasha Heather","doi":"10.1017/thg.2025.10033","DOIUrl":"https://doi.org/10.1017/thg.2025.10033","url":null,"abstract":"<p><p>This position statement provides guidelines for health professionals who are considering online or direct-to-consumer genetic testing for their patients. It presents the major issues around online and direct-to-consumer (DTC) testing including how it is accessed, motivations for accessing testing and how to return these results. Online or DTC recommendations include: (1) DTC testing should only be done by individuals/consumers who are well informed, aware of the risks, benefits and limitations of testing, and able to consent for their DNA to be collected, analyzed and potentially stored. Where possible, individuals/consumers should also be aware of the alternative option of undertaking testing through healthcare professionals in a clinical context, and the benefits of this. (2) Decisions about having a child tested should be based on peer-reviewed, published evidence. Genomics testing for children should be within a clinical context where parents are informed, have access to clinical support and professional genetic counseling about this decision, as well as support for the range of results received. (3) Parents considering direct-to-consumer testing on their newborn are counselled, or given information, to encourage them to have standard government funded newborn bloodspot screening testing on their newborn. (4) When choosing an online genomic test, preference should be given to tests undertaken in accredited laboratories offering tests accredited with the Therapeutic Goods Administration. (5) Results obtained through methods other than direct analysis from a laboratory accredited to perform genomic testing to inform human health and wellbeing should be interpreted with caution. The HGSA recommends that such results must be confirmed in an accredited diagnostic laboratory prior to relying on them to inform options for treatment, surveillance or risk reduction, or before undertaking cascade testing in family members. (6) When individuals are concerned about their health, they should consult an appropriate healthcare professional to decide whether an online genomic test is appropriate and discuss how useful test results could be to make health-related decisions.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805223","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 Interplay of Genes and Environment Across Multiple Studies (IGEMS) Consortium After Fifteen Years.","authors":"Deborah Finkel, Brian K Finch, Margaret Gatz, Kaare Christensen, Carol E Franz, Ida K Karlsson, William S Kremen, Robert F Krueger, Michelle Lupton, Nicholas Martin, Matt McGue, Miriam A Mosing, Jenae Neiderhiser, Marianne Nygaard, Elizabeth Prom-Worley, Chandra Reynolds, Perminder Sachdev, Elina Sillanpää, Eero Vuoksimaa, Keith E Whitfield, Orla Hayden, Ellen Walters, Nancy L Pedersen","doi":"10.1017/thg.2025.10036","DOIUrl":"10.1017/thg.2025.10036","url":null,"abstract":"<p><p>The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 21 twin studies from 5 countries (Australia, Denmark, Finland, Sweden, and United States) established to explore the nature of gene-environment interplay in cognitive, physical, and emotional health across the adult lifespan. The combined data from over 145,000 participants (aged 18 to 108 years at intake) has supported multiple research projects over the three phases of development since its inception in 2010. Phases 1 and 2 focused on launching and growing the consortium and supported important developments in data harmonization, analyses of data pooled across multiple studies, incorporation of linkages to national registries and conscription data, and integration of molecular genetic and classical twin designs. IGEMS Phase 3 focuses on developing appropriate infrastructure to maximize utilization of this large twin consortium for aging research.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.2,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turner's Syndrome in Discordant Dizygotic Twins: Biological Origins and Twin Relations/Twin Research Reviews: Prevention of Premature Twin Birth; Twin Gestation with Hydatidiform Mole; Update on Feingold Syndrome Twins; Qualitative MZ Twin Difference Studies/Media: Identical Twins Turn 100 Years of Age; Twins in Famous Families; Celebration of Yorùbá Twins of Nigeria; Identical Artistic Partners; Rare Conjoined Twins Separated.","authors":"Nancy L Segal","doi":"10.1017/thg.2025.10034","DOIUrl":"https://doi.org/10.1017/thg.2025.10034","url":null,"abstract":"<p><p>A pair of dizygotic (DZ) twins discordant for Turner syndrome are discussed with reference to the biological origins of the condition and the effects of discordance on the twin relationship. There is little research on how having an atypical twin influences the life events and goals of the typical twin. Next, timely reviews of research on preventing premature twin birth, a twin gestation with hydatidiform mole, an update on Feingold syndrome twins discussed in a previous issue of this journal, and qualitative monozygotic twin difference studies are presented. The final portion of this article covers human interest stories of twins that are variously entertaining and enlightening. They include identical twins who celebrated their 100th birthday together, twins in famous families, celebration of the Yorùbá twins of Nigeria, identical artistic partners, and surgical separation of a rare, conjoined twin set.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669276","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":"Genetics, Diet or Divine Blessing? Local and Scientific Explanations for High Dizygotic Twinning in Igbo-Ora, Nigeria.","authors":"Akinwale Fadoju","doi":"10.1017/thg.2025.10029","DOIUrl":"https://doi.org/10.1017/thg.2025.10029","url":null,"abstract":"<p><p>Igbo-Ora, a town in southwestern Nigeria, is renowned for exceptionally high dizygotic twin birth rates, recording approximately 45 per 1000 live births. This article explores the factors behind this unique phenomenon by critiquing the community's perceptions and narrative of the factors responsible for the high twinning rate and comparing these perceptions with biomedical hypotheses. Drawing on 6 months of ethnographic fieldwork - participant observation, 81 semistructured interviews, and FGDs - this study documents local narratives that highlight hereditary 'twin threads' -; specific foods, notably Ilasa (okra-leaf soup) and cassava meals; environmental qualities of 'air' and 'water'; and divine sanction as factors responsible for the incidence of twin birth in Igbo-Ora. These local narratives are analyzed against certain biomedical perspectives on maternal age and parity effects, putative genetic variants influencing gonadotrophins, and dietary phytoestrogens. The study found that the community resist single-cause explanations for the incidence of twin birth and instead articulates a complementarity of genetic, ecological, dietary, and spiritual factors. This holistic framing contrasts with and complements prevailing genetic and nutritional theories surrounding the incidence of twin birth. The article argues that future genetic and epidemiological investigations in high-twinning populations must be culturally attuned to ensure accurate phenotype definition, ethical engagement, and translational relevance.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640115","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 - ERRATUM.","authors":"Vegard F Skirbekk, Bernt Bratsberg, Christian M Page, Dana Kristjansson","doi":"10.1017/thg.2025.10023","DOIUrl":"https://doi.org/10.1017/thg.2025.10023","url":null,"abstract":"","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1"},"PeriodicalIF":1.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483029","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":"An Exploration of the Genetic Architecture of Pregnancy-Related Linea Nigra and Its Relationship With Pigmentation Phenotypes.","authors":"Svetlana Bivol, Mathias Seviiri, Lucía Colodro-Conde, Brittany L Mitchell, Catherine M Olsen, David C Whiteman, Matthew H Law, Penelope A Lind, Jodie N Painter, Sarah E Medland","doi":"10.1017/thg.2025.10026","DOIUrl":"https://doi.org/10.1017/thg.2025.10026","url":null,"abstract":"<p><p>Human eye, skin and hair color pigmentation are highly heritable traits influenced by hundreds of genetic loci. The heritability and genetic etiology of the hyperpigmentation trait pregnancy-related linea nigra (PLN), where a dark but usually temporary vertical line develops on the abdomen, is unknown, and our understanding of its relationships with other pigmentation traits is limited. We conducted a genetic study of self-reported PLN in women of European ancestry, using a genome-based restricted maximum likelihood (GREML) method to estimate PLN heritability, performing a genomewide association study (GWAS) to explore the genetic factors underlying PLN, and calculating polygenic risk scores (PRS) to assess whether this trait shares genetic liability with two other skin pigmentation phenotypes, skin colour and mole count. We found 35% of the variance in developing PLN was explained by common genetic variation. The GWAS revealed four genomic loci suggestively associated (<i>p</i> values ≤ 1 × 10^-6) with PLN: rs1263154 near the <i>UPP2</i> gene (<i>p</i> = 9.0 × 10^-7), rs26331 near <i>SEMA6A</i> (<i>p</i> = 6.6 × 10^-7), rs78371540 in <i>OLFM3</i> (<i>p</i> = 5.5 × 10^-7), and rs72693263 near <i>FLRT2</i> (<i>p</i> = 1.1 × 10^-7). Of these genes only <i>OLFM3</i> has been previously associated with pigmentation. Our PRS results provide the first evidence that genetic factors underlying skin color and mole count also contribute to the development of PLN in women of European ancestry.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439167","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":"Heritability Estimates from Twin Studies: The Efficiency of the MZA Design.","authors":"David T Lykken, Seymour Geisser, Auke Tellegen","doi":"10.1017/thg.2025.10022","DOIUrl":"https://doi.org/10.1017/thg.2025.10022","url":null,"abstract":"<p><p>The most accurate confidence intervals for estimates of heritability are based on Fisher's Z-transformation. Using these methods, Loehlin and Nichol's (1976) analysis is confirmed, <i>viz</i>., that it is pointless to estimate heritabilities from the classical twin method unless one is prepared to recruit upwards of 800 twin pairs for study. Even then the assumptions of that method are so improbable as to leave reasonable doubt about the true value of H. Estimates of H from the correlation of monozygotic twins reared apart (MZA twins), on the other hand, is remarkably more stable than that obtained by comparing MZ with DZ correlations. Moreover, estimates of H based on the MZA design rest upon more reasonable (and often testable) assumptions.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356070","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":"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}