European Journal of Human Genetics最新文献

{"title":"'Everyday genetics' in the Mass Observation Project: insights on genetics from people writing for an archive of everyday life in Britain.","authors":"Rachel Horton, Susie Weller, Lisa Ballard, Anneke Lucassen","doi":"10.1038/s41431-026-02113-x","DOIUrl":"https://doi.org/10.1038/s41431-026-02113-x","url":null,"abstract":"<p><p>Over the past two decades, genetic testing has undergone major shifts in its accessibility and in its nature. Historically, it primarily involved analysis of single genes selected on the basis of symptoms or family history, and was available only to a few. Now, options range from diagnostic clinical genomic tests, to broader screens offered to 'healthy' populations, to direct-to-consumer tests offering to explore ancestry. As genetic testing becomes an increasingly 'everyday' encounter, we sought to explore how the topics of genetics (and genomics) were considered in the Mass Observation Project, an archive of writing by 'ordinary' people about everyday life in Britain. 55% of the 147 respondents had personal experience of genetic testing or knew someone who had, typically to explore ancestry. Responses often gave the sense of genetic testing as a powerful tool in healthcare with results that were fairly definitive. Genomic testing was typically written about as an amplification of genetic testing, generating information of similar solidity. Writers threaded together personal experiences with insights drawn from a wide variety of media, often quite old, in outlining their ideas. While many positioned genetics as outside their remit, respondents engaged in depth with the opportunities and challenges raised, advocating for ethical/societal considerations to form a key part of decision-making regarding genetics. Our analysis shows that people without prior experience of clinical genetic testing may yet have a wealth of experiences and exposures sculpting their expectations as to what testing stands to bring. Consent conversations may benefit from exploring these.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access alone does not define equity in reproductive genetics.","authors":"Asha N Talati, Amy Mottola, Neeta L Vora","doi":"10.1038/s41431-026-02115-9","DOIUrl":"https://doi.org/10.1038/s41431-026-02115-9","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Public perceptions of genetic sequencing in China: barriers and drivers of adoption.","authors":"Liyong Lu, Shan Jiang, Yuan Wang, Sidong Liu, Jiao Lu, Yuanyuan Gu","doi":"10.1038/s41431-026-02109-7","DOIUrl":"https://doi.org/10.1038/s41431-026-02109-7","url":null,"abstract":"<p><p>This study explores public attitudes toward genetic sequencing (GS) services in China and identifies key factors influencing adoption. Although GS has the potential to strengthen precision public health, its uptake may be constrained by societal and attitudinal barriers. We used a sequential mixed-methods design, combining focus group discussions with a structured ranking questionnaire. A total of 28 participants (mean age 48.9 years) were included. The qualitative analysis identified five major themes reflecting participants' understanding, concerns, and expectations regarding GS. Quantitatively, the most influential factors for adoption were the characteristics of genomic information and financial accessibility. Demographic differences were observed: men prioritized cost, whereas women emphasized clarity of information; older adults focused on affordability, whereas younger participants valued transparency and the utility of information. Psychological concerns also emerged as an important barrier, including fears of genetic discrimination and emotional distress arising from the implications of genetic information. In contrast to European studies that often highlight privacy and data protection, participants in this study placed greater emphasis on informational and financial considerations. Despite the modest sample, thematic saturation was reached and the mixed-methods approach provides complementary qualitative and quantitative evidence. Addressing public concerns through transparent communication, education, psychological support, and affordability-focused policies will be important to facilitate integration of GS into healthcare systems. These findings provide culturally grounded evidence to inform precision public health in China and similar contexts.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study identifies protective genetic factors in active blood donors against multiple diseases.","authors":"Jonna Clancy, Jarkko Toivonen, Jouni Lauronen, Jukka Partanen, Mikko Arvas, Jarmo Ritari","doi":"10.1038/s41431-026-02100-2","DOIUrl":"https://doi.org/10.1038/s41431-026-02100-2","url":null,"abstract":"<p><p>The healthy donor effect (HDE) refers to the lower mortality observed among blood donors compared to the general population. While HDE arises due to healthier individuals being more likely to donate, the extent to which it is influenced by genetic differences remains unclear. To elucidate the genetic basis of HDE, we conducted a genome-wide association study (GWAS) involving 53,688 active blood donors with extensive donation histories and 228,060 controls from biobank cohorts within the FinnGen project. We identified 46 fine-mapped genome-wide significant loci associated with several health-related endpoints, plasma protein levels and laboratory measurements. Genetic correlation analyses across FinnGen endpoints revealed that blood donors are genetically protected against several diseases beyond those affecting donation eligibility. Using the correlated endpoints as exposures in multivariable Mendelian randomization (MVMR) to inform priors for Bayesian GWAS, we found that 25 of the fine-mapped loci exert a direct effect on blood donorship (BD) rather than acting through disease mediation, suggesting a genetic contribution to maintaining a health state conducive to long-term donation. We also performed MVMR analyses of laboratory traits. The results indicated that normal liver function, blood glucose, and low inflammation independently increase the likelihood of becoming a blood donor, while iron levels showed no causal relationship. Functional enrichments among the proteins regulated by the 46 fine-mapped variants included mainly red cell antigen-related cell adhesion processes. In conclusion, our findings demonstrate that HDE is partly explained by genetic factors, involving both direct health-promoting effects and indirect eligibility selection.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetics of the circle of Willis come full circle.","authors":"Miriam E Quinlan, Paul A Nyquist","doi":"10.1038/s41431-026-02112-y","DOIUrl":"https://doi.org/10.1038/s41431-026-02112-y","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunistic genomic screening of healthy controls in an Australian biobank.","authors":"Lucas A Mitchell, Mary-Anne Young, Thomas Ohnesorg, Matthew Hobbs, Joseph Copty, Jaye S Brown, Alex W Hewitt, Joseph E Powell, Daniel G Macathur, Amanda M Willis","doi":"10.1038/s41431-026-02104-y","DOIUrl":"https://doi.org/10.1038/s41431-026-02104-y","url":null,"abstract":"<p><p>Leveraging existing genomic data to opportunistically screen for secondary findings (SFs) can identify individuals at increased genetic risk who may be missed by criteria-based testing. While some guidelines support returning actionable SFs with professional support, there is a gap in consistent practice regarding the return process. This study reports the outcomes of opportunistic genomic screening in an Australian biobank. Whole genome sequencing data from 1057 healthy participants in the Tasmanian Ophthalmic Biobank (TOB), all of white European ancestry, underwent opportunistic screening for pathogenic (P) or likely pathogenic (LP) variants affecting genes in the ACMG SF v3.0 list. Variants of interest were manually curated, and only P/LP variants were returned. Actionable SFs (P/LP variants) were identified in 3.6% (38/1057) of participants. The most common genes were HFE (haemochromatosis), LDLR (Familial Hypercholesterolemia), and TP53 (Li-Fraumeni syndrome). Of the 38 participants with a variant, 27 received their result, with two-thirds being newly informed. Ten participants were referred to clinical genetics for diagnostic confirmation, while seven declined to proceed. Opportunistic screening identified a clinically significant incidence of actionable SFs in a healthy biobank cohort. There was high participant interest in receiving results, although subsequent uptake of clinical referral remains a challenge.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy experiences of expectant parents with Neurofibromatosis type 1: a qualitative interview study.","authors":"Gamze Kaplan, Debbie M Smith, Ming Wai Wan, Hannah Slevin, Emma Burkitt-Wright, Shruti Garg","doi":"10.1038/s41431-026-02099-6","DOIUrl":"https://doi.org/10.1038/s41431-026-02099-6","url":null,"abstract":"<p><p>Pregnancy in the context of Neurofibromatosis 1 (NF1) may be emotionally complex due to uncertainties surrounding inheritance and the condition's variable presentation. This study aimed to explore how expectant parents with NF1 experience pregnancy and relate to their unborn child. Fourteen participants took part in individual semi-structured interviews, and data were analysed using reflexive thematic analysis. Participants described how decisions around conception and genetic testing were influenced by personal and medical history, perceived severity of NF1, and concerns about potential impact on their child. Participants described how ongoing uncertainty contributed to feelings of anxiety, guilt, and emotional restraint, which they managed through internal strategies such as seeking reassurance, information, and acceptance, as well as through external support networks. Notably, internal representations of the unborn child were sometimes shaped by cautious and emotionally regulated engagement in response to uncertainty. In a condition like NF1, where uncertainty may complicate prenatal bonding, adapting psychological interventions that have been used antenatally to promote early bonding and support later parenting outcomes could help strengthen emotional wellbeing and the developing parent-infant relationship.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting penetrance in an era of genomic screening.","authors":"Leigh Jackson, Caroline F Wright","doi":"10.1038/s41431-026-02101-1","DOIUrl":"https://doi.org/10.1038/s41431-026-02101-1","url":null,"abstract":"","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting LSDMCA: male lethality escape and genotype-phenotype correlations.","authors":"Alfonso Manuel D'Alessio, Alessia Indrieri, Giuseppina Vitiello, Manuela Morleo, Susan Schelley, Gregory M Enns, Chiara Passarelli, Roberta Tammaro, Valeria Tiranti, Camille Peron, Wallid Deb, Antonio Novelli, Bertrand Isidor, Achille Iolascon, Brunella Franco","doi":"10.1038/s41431-026-02098-7","DOIUrl":"https://doi.org/10.1038/s41431-026-02098-7","url":null,"abstract":"<p><p>Mitochondrial disorders (MDs) are a diverse group of genetic conditions primarily affecting the oxidative phosphorylation (OXPHOS) system and cellular energy production. Among MDs, Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), or Microphthalmia with Linear Skin Lesions (MLS) syndrome, is a rare X-linked dominant male-lethal disorder characterized by ocular malformations, linear skin defects, and multisystem developmental anomalies. These features are associated with pathogenic variants in genes related to mitochondrial function, including HCCS, COX7B, and NDUFB11 or chromosomal rearrangements of the Xp22 region encompassing HCCS. Despite progress, genotype-phenotype correlations remain insufficiently defined. In this study, we report three novel mutations in three patients with LSDMCA, broadening the phenotypic spectrum of the disorder. Whole exome sequencing revealed pathogenic missense variants in HCCS [NM_005333.5: c.625 G > C; p.(Asp209His)] and COX7B [NM_001866.3: c.221 C > T; p.(Pro74Leu)] in two unrelated patients. Functional studies confirmed that the COX7B variant impairs mitochondrial respiratory chain (MRC) function. A third patient harbored a novel frameshift pathogenic variant in NDUFB11 [NM_001135998.3: c.145_152dup; p.(Thr52Glnfs*66)], further implicating mitochondrial dysfunction in LSDMCA pathogenesis. Notably, the COX7B variant was identified in a biological male (46, XY) without X-chromosome structural rearrangements, marking the first such reported case of LSDMCA. Our data suggest that certain missense variants, resulting in mild impairment of the gene product, may allow male survival, thereby expanding the known phenotype of this rare disorder. This report advances our understanding of genotype-phenotype correlations in LSDMCA and highlights the impact of mitochondrial dysfunction during embryonic development.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene x environment interaction analysis confirms genetic modifier effects on steroid efficacy via TGF-β pathway in Duchenne muscular dystrophy.","authors":"Veronica J Vieland, Sang-Cheol Seok, Megan A Waldrop, Leigh M Gabel, Diane M Dunn, Kevin M Flanigan, Robert B Weiss","doi":"10.1038/s41431-026-02110-0","DOIUrl":"https://doi.org/10.1038/s41431-026-02110-0","url":null,"abstract":"<p><p>This paper continues our development of methods for discovery of genetic modifiers of the Duchenne muscular dystrophy (DMD) phenotype. DMD is an X-linked recessive disorder involving progressive muscle tissue loss with replacement by fat and fibrotic tissue, leading in most cases to loss of ambulation (LOA) by early to mid-adolescence. The standard pharmacologic treatment is corticosteroid administration, which increases average LOA by 2-3 years. There is variation in LOA due to specific DMD mutations, some of which permit the production of residual or partial dystrophin protein and lead to milder phenotypes. But there is also believed to be variation due to genetic modifiers acting even in patients whose DMD mutations preclude dystrophin production altogether, based in part on animal models, and several genes have been implicated as potential modifiers of LOA in DMD patients. Here we consider whether the mechanism of action of any of these genes might be to influence LOA by modifying the effects of corticosteroid exposure. We develop and evaluate a novel statistic, the PPI_GxE; we consider the issue of potential \"phenocopies,\" or individuals whose late LOA might be due to residual dystrophin production; and we apply our approach to 12 candidate SNPs using our DMD dataset. We find evidence of genotype x steroid interaction effects for 4 out of the 12 SNPs we tested, which can be linked to the TGF-β pathway. These results corroborate the hypothesis that modifiers in the TGF-β pathway affect LOA by modulating the efficacy of corticosteroid administration.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}