Twin Research and Human Genetics最新文献

{"title":"Identifying Potential Drug Targets for Treating ADHD From a Genetic Perspective: A Mendelian Randomization Study.","authors":"Pei Pei, Shuwen Lu, Weijie Yu, Xiaoyu Zhao, Jiannan Lin","doi":"10.1017/thg.2026.10106","DOIUrl":"https://doi.org/10.1017/thg.2026.10106","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Current pharmacological treatments have limitations, highlighting the need for new therapeutic targets. Using two-sample Mendelian randomization with cis-expression quantitative trait loci from the eQTLGen Consortium (31,684 individuals), we performed genomewide analysis against ADHD genomewide association study summary statistics from European ancestry (20,183 cases; 35,191 controls) and FinnGen R10 (2,788 cases; 405,153 controls). Genetic instruments were selected at <i>p</i> < 5 × 10^-8 with <i>F</i>-statistic > 10 and linkage disequilibrium clumping (<i>r</i>² < .001). Mendelian randomization estimates were derived using inverse-variance weighted, weighted-median, and Mendelian randomization-Egger methods, with leave-one-out sensitivity analysis. Colocalization was performed to distinguish causality from linkage disequilibrium. From 5430 genes with valid instruments, we identified 10 ADHD-associated genes (inverse-variance weighted <i>p</i> < .01, consistent direction across methods): four risk-increasing genes (<i>RRAGD, DTX2, HMOX1, AGAP3</i>) and six protective genes (<i>NUCKS1, CPSF1, MAU2, CLDN5, CYP4F12, ATP6V1E2</i>). <i>MAU2</i> demonstrated strong colocalization support (posterior probability for hypothesis 4 > .6). Pathway enrichment highlighted mechanistic target of rapamycin signaling as a priority mechanism. Computational in silico drug prioritization nominated candidate compounds (e.g., selenium, ketoconazole) predicted to modulate these targets. This study identifies genetically supported therapeutic targets for ADHD. <i>MAU2</i> emerged as the most promising causal locus. Rapamycin signaling represents a key mechanistic pathway. Several repositioned candidates (e.g., selenium, ketoconazole) warrant further experimental evaluation as potential leads. These findings provide a hypothesis-generating foundation for drug target prioritization, and require functional confirmation in CNS models and clinical validation before therapeutic relevance can be established.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184560","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":"Are Socioeconomic Status and Time in Preschool Mediators of Shared Environment Variance in Reading Ability?","authors":"Emily Carver, William Coventry, Stephen Petrill, Robin Corley, Stefan Samuelsson, Richard Olson, Brian Byrne","doi":"10.1017/thg.2026.10099","DOIUrl":"https://doi.org/10.1017/thg.2026.10099","url":null,"abstract":"<p><p>While socioeconomic status (SES), time in preschool (TiP) and their interaction are related to reading ability, the results have been mixed. This study assessed whether the shared environment mediated these associations using a longitudinal behavior genetic design. Further, this study contrasted the source of variance in reading accounted for by (a) SES and TiP, against that of (b) genes, the shared environment, and the unique environment. Participants were 511 monozygotic twin pairs, and 515 dizygotic same-sex twin pairs from Australia, the United States and Scandinavia. They were assessed at preschool, kindergarten, grade 1, and grade 2. The interaction between TiP and SES did not explain variance in reading at any stage. At preschool, SES and TiP combined accounted for 9% of the total variance in reading, or 17.6% of the shared environment variance. Of that 9%, SES explained 8.1% independent of TiP. By Grade 2, SES and TiP explained 4% of the total variance, or 57% of the shared environment variance. Of that 4%, SES accounted for 3% with TiP accounting for just 1%. It was found that SES, but not TiP, had a small but significant influence on reading over time, and is a substantial mediator of the shared environment influence of reading by Grade 2.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172317","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":"Estimating the Heritability of Intelligence with a Nuclear Twin Family Design.","authors":"Kate Wyllie, William Coventry, Burt Hatch, Glen van der Vyver","doi":"10.1017/thg.2026.10096","DOIUrl":"https://doi.org/10.1017/thg.2026.10096","url":null,"abstract":"<p><p>Intelligence, and the favorable life outcomes with which it is associated, are not shared equally between individuals or groups. In an endeavor to better understand the inequality, behavioral genetics (BG) have employed the classical twin design (CTD) to apportion the variability in the intelligence quotient (IQ) to genetic and environmental sources. Recent research has revealed that such parameter estimates are subject to bias: underestimating the influence of assortative mating, and nonadditive genetic effects. These biases are somewhat mitigated by the nuclear twin family design (NTFD). To date no published studies have applied the NTFD to IQ. This study addresses this limitation utilizing a meta-analysis of data comprising IQ measures from 660,365 twin, parent-child, and spousal pairs collected over more than 50 years from more than 15 countries. In a comparison of parameter estimates obtained under the CTD and NTFD, this study confirmed that the NTFD more accurately estimated the heritability of IQ. These findings will inform and guide future research, gene-mapping efforts, and public policy aimed at correcting the inequality in educational and life outcomes that are significantly associated with IQ.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171691","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 With Feingold Syndrome: Overview and Interview/Twin Research Summaries: Pseudoamonoamniotic Twins; Selective Fetal Growth Restriction in Monoamniotic Twins; Twin Authorship Attribution; Twins Discordant for Clubfoot/Human Interest: Twins with Different Fathers; Biological Relatedness in a Married Couple; Birth of Identical Quadruplets; Twins Switching Places - CORRIGENDUM.","authors":"Nancy Segal","doi":"10.1017/thg.2026.10103","DOIUrl":"https://doi.org/10.1017/thg.2026.10103","url":null,"abstract":"","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1"},"PeriodicalIF":1.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081850","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":"Twin Conferences Come in Pairs: Views from Brazil/Twin Research Reviews: Discordant Transgenderism in African Twins; Attachment in Twin Families; Tactile Sensitivity in Twins; Self-Employed Twins and Stress; Note on Chimerism/Human Interest Items: Artistic Twinships; Naturally Conceived Identical Quadruplets; Sports Award for a Deceased Co-Twin; New Prenatal Procedure Saves Twins; World's Most Premature Pair.","authors":"Nancy L Segal","doi":"10.1017/thg.2026.10101","DOIUrl":"https://doi.org/10.1017/thg.2026.10101","url":null,"abstract":"<p><p>This article summarizes events at two June 2026 twin conferences held in different Brazilian cities. The first one took place at the State University of Londrina, in the state of Paraná; the second one took place at the University of São Paulo, in the state of São Paulo. This section is followed by reviews of research concerning discordant transgenderism in African twins, attachment in twin families, tactile sensitivity in twins, stress among self-employed twins, and chimerism in dizygotic twins. The final portion of the article presents human interest items that both inform and entertain. They include artistic twinships, naturally conceived identical quadruplets, sports recognition for a deceased twin athlete, a new prenatal life-saving procedure for twins, and the world's most premature pair.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-6"},"PeriodicalIF":1.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081880","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":"Fetal Growth Disorders in Dichorionic Diamniotic IVF Twin Pregnancies: A Retrospective Longitudinal Cohort Study.","authors":"Semir Köse, Çağlasu Sancaktar, Alper Biler, Ümit İnceboz","doi":"10.1017/thg.2026.10093","DOIUrl":"https://doi.org/10.1017/thg.2026.10093","url":null,"abstract":"<p><p>Growth disorders are common in in vitro fertilization (IVF)-conceived twins, but risk factors specific to dichorionic-diamniotic twins remain incompletely characterized. This study aimed to assess these risk factors. Data from in vitro fertilization pregnancies (December 2020 - November 2024) were retrospectively analyzed. Small for gestational age was defined as estimated fetal weight below the 10th percentile. Intertwin discordance greater than 15% was considered significant. Change in uterine artery pulsatility index was calculated by subtracting first-trimester from second-trimester values. Of 169 dichorionic-diamniotic twin pregnancies, 30 (17.8%) were from fresh embryo transfer and 139 (82.2%) from frozen embryo transfer. Mean uterine artery pulsatility index was higher in the fresh group in both trimesters (first: 1.72 vs. 1.30; second: 0.91 vs. 0.78; both <i>p</i> = .001). Small for gestational age incidence was similar between groups (56.7% vs. 50.3%, <i>p</i> = .441), as was significant discordance (36.6% vs. 25.9%, <i>p</i> = .081). Logistic regression identified advanced maternal age (odds ratio: 1.07, 95% CI [1.00, 1.14]; <i>p</i> = .024), higher first-trimester uterine artery pulsatility index (<i>OR</i> 2.19, 95% CI [1.27, 3.76]; <i>p</i> = .002), and preeclampsia (<i>OR</i> 3.74, 95% CI [1.19, 11.67]; <i>p</i> = .023) as predictors of small for gestational age. For significant discordance, predictors were second-trimester intertwin estimated fetal weight difference (<i>OR</i> 1.03, 95% CI [1.01, 1.04]; <i>p</i> = .001) and change in uterine artery pulsatility index (odds ratio: 2.51, 95% CI [1.01, 6.22]; <i>p</i> = .047). Uterine artery pulsatility index and second-trimester biometric differences independently predict small for gestational age and intertwin discordance in IVF-conceived dichorionic-diamniotic twin pregnancies.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081615","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":"Can Depression Polygenic Risk Score Predict Postinfective Fatigue Syndrome (PIFS) in the Dubbo Infection Outcomes Study (DIOS)?","authors":"Albena G Ruseva, Braulio M Valencia, Scott D Gordon, Andrew Lloyd, Ian B Hickie, Nicholas Martin","doi":"10.1017/thg.2026.10098","DOIUrl":"https://doi.org/10.1017/thg.2026.10098","url":null,"abstract":"<p><p>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 <i>OR</i> = 0.99, 95% CI [0.78, 1.26], <i>p</i> = .95) nor CFS-PGS (adjusted <i>OR</i> = 0.97, 95% CI [0.77, 1.23], <i>p</i> = .81) predicted PIFS diagnosis. In exploratory analysis, the MDD-PGS × sex interaction was suggestive (Wald <i>p</i> = .06; Firth penalized <i>p</i> = .04), with higher MDD-PGS associated with increased odds of PIFS in women but decreased odds in men. The CFS-PGS × 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.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-7"},"PeriodicalIF":1.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025609","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":"J. B. S. Haldane's Cost of Natural Selection and an Intervention by William Feller.","authors":"Alan Stark","doi":"10.1017/thg.2026.10092","DOIUrl":"https://doi.org/10.1017/thg.2026.10092","url":null,"abstract":"<p><p>Haldane (J. B. S.) was a brilliant scientist. His 'cost of natural selection' is a view of the dark underbelly of Darwin's creation - a count of the individuals who fall by the wayside when one allele displaces another. Th. Dobzhansky, perhaps not liking Haldane's brand of mathematics, called in the eminent European William Feller to scrutinize Haldane's cost. Feller published two articles (1966, 1967). The second sentence of the first paper shows that Feller misunderstood what Haldane measured: 'These authors [Haldane and M. Kimura] introduce a measure for the loss in population size caused by a slow natural selection.' Feller made intricate calculations of population size under various assumptions. These missed the point of Haldane's clever notion. Feller's two articles are an attempted demolition of conventional population genetics methodology.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"1-3"},"PeriodicalIF":1.3,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702582","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":"Neonatal Health and Long-Term Outcomes: Twin-Based Evidence From Linked Scandinavian Registers.","authors":"Gabriella Conti, Aline Buetikofer, Evelina Bjorkegren, Marten Palme, Kjell G Salvanes","doi":"10.1017/thg.2026.10095","DOIUrl":"10.1017/thg.2026.10095","url":null,"abstract":"<p><p>This study examines the long-term consequences of neonatal health using three birth anthropometric measures - weight, length, and head circumference - and analyzes their differential associations with outcomes across the life course. Using linked Swedish and Norwegian population registers with follow-up into adulthood, we compare birth measures of singletons and twins and further estimate within-twin-pair fixed-effects models that control for shared genetic and family environmental factors. Our samples comprise up to approximately 679,000 singletons and 10,400 twins in Sweden, and 347,841 singletons and 6,762 twins in Norway, followed into adulthood. We find that different birth measures capture distinct aspects of fetal development with varying predictive validity across outcome domains. Birth length emerges as the strongest predictor of health outcomes (infant mortality, adult height), consistent with its role as a cumulative indicator of skeletal growth throughout gestation. Birth weight retains stronger associations with cognitive and educational outcomes (grade point average [GPA], years of schooling) in conditional models. Head circumference shows weak and inconsistent associations across specifications. Using within-pair head circumference differences to classify twins as symmetrically versus asymmetrically growth restricted, we find that symmetric intrauterine growth restriction is associated with substantially worse long-term outcomes than asymmetric restriction. In Norwegian twin pairs, growth restriction is associated with lower general cognitive ability (measured at military enlistment) relative to the unaffected co-twin; this within-pair deficit is more than twice as large for symmetric as for asymmetric restriction. We also document significant intergenerational transmission of birth anthropometrics, suggesting both environmental and genetic contributions. Finally, our register-based design with near-complete population coverage minimizes selection bias and attrition while providing statistical power for within-pair analyses across multiple outcomes. Exclusive reliance on birth weight may obscure important information about early-gestation developmental insults.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"323-333"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081862","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":"Record Linkage as a Tool for Expanding Research Opportunities: Insights from the Netherlands Twin Register and National Health and Population Data in the Netherlands.","authors":"Veronika V Odintsova, Susanne Bruins, Camiel M van der Laan, Dorret I Boomsma","doi":"10.1017/thg.2026.10070","DOIUrl":"10.1017/thg.2026.10070","url":null,"abstract":"<p><p>Record linkage projects provide powerful opportunities to enrich cohort data with administrative and clinical information from national registries. The Netherlands Twin Register (NTR) is a large population-based twin-family cohort with longitudinal data collection that has established multiple record linkage initiatives to expand research on genetic and environmental determinants of health, disease, behaviour, development, and fertility. In this article we summarize and discuss NTR record linkage projects. Clinical and pathology registries have provided essential data on chorionicity, reproductive history, neonatal thyroid function, and cancer diagnoses, facilitating studies on prenatal environment, disease heritability, and polygenic risk prediction for diseases. Linkage with health insurance data has enabled validation of medication use and health research. Collaborations with Statistics Netherlands allow linkage to nationwide population-based data via secure infrastructures such as Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI), supporting genomewide association studies of, for example, healthcare expenditure. Finally, linkage to environmental exposure datasets has permitted exposomewide analyses of health and wellbeing. Together, these projects illustrate the feasibility, scientific value, and challenges of record linkage in the Dutch context, highlighting its role in advancing twin research, genetic epidemiology, and population health studies.</p>","PeriodicalId":23446,"journal":{"name":"Twin Research and Human Genetics","volume":" ","pages":"279-290"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989219","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}