European Journal of Human Genetics最新文献

{"title":"Modeling the long-range effect of an inversion downstream of EFNB1 concludes a 43-year molecular diagnostic odyssey for craniofrontonasal syndrome.","authors":"Dong Li, Leticia S Matsuoka, Sarah Donoghue, Cuiping Hou, Alanna Strong, Donna M McDonald-McGinn, Linton Whitaker, Jesse Taylor, Elizabeth J Bhoj, Hakon Hakonarson, Elaine H Zackai","doi":"10.1038/s41431-025-01887-w","DOIUrl":"https://doi.org/10.1038/s41431-025-01887-w","url":null,"abstract":"<p><p>Craniofrontonasal syndrome (CFNS; MIM #304110) is a rare craniofacial disorder characterized by hypertelorism, a broad nasal root with a bifid nasal tip, orofacial clefting, and genital malformations caused by pathogenic variants in the X-linked gene EFNB1 (MIM *300035). CFNS exhibits sex-specific heterogeneity, with increased severity in females likely secondary to cellular interference related to random X-inactivation, resulting in mosaic EFNB1 expression. Previous studies have identified over 140 variants in EFNB1, but approximately 20% of CFNS have negative molecular testing, either due to a yet undiscovered causal gene or causal variants in regulatory regions not covered by traditional genetic testing methodologies. Here, we report a two-generation family with a clinical diagnosis of CFNS and negative clinical molecular testing. Research short-read genome testing identified a 2-Mb inversion together with two smaller deletions (13- and 7-bp), about 106-Kb downstream of EFNB1, which cosegregated with CFNS. Patient-derived fibroblasts reprogrammed into induced pluripotent stem cells (iPSCs) demonstrated two distinct iPSC populations in affected females, where one or other of the two X chromosomes was inactivated. In vitro assays further demonstrated that iPSCs with the active X chromosome bearing the inversion, exhibited a significant increase in EFNB1 expression, suggesting allelic imbalance contributes to mosaic EFNB1 expression. These findings nominate a novel causal variant type of CFNS, conclude a 43-year diagnostic odyssey for an affected family, and offer new hope for family planning for affected individuals.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257705","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":"Developing genetic literacy in high school students with intellectual disability: Teachers' experiences and perspectives.","authors":"Karen-Maia Jackaman, Iva Strnadová, Sierra Angelina Willow, Julie Loblinzk Refalo, Jackie Leach Scully, Elizabeth Emma Palmer, Bronwyn Terrill","doi":"10.1038/s41431-025-01865-2","DOIUrl":"https://doi.org/10.1038/s41431-025-01865-2","url":null,"abstract":"<p><p>Genetics is a rapidly evolving field with the potential to achieve improved health outcomes through precision medicine. People with intellectual disability have asked to know more about genetic conditions that they may have, but require education to build their genetic literacy, thereby empowering them to make informed healthcare decisions. Key to this is ensuring students with intellectual disability can access and participate in genetics education at school. Despite integration of genetics into curriculum, little is known about whether teachers are equipped to engage students with intellectual disability with this content. To explore this issue, fifteen teachers who teach genetic content to students with intellectual disability participated in semi-structured interviews or in a focus group. The analysis revealed three interconnected themes addressing genetics education for students with intellectual disability. These themes encompassed effective pedagogical approaches and curriculum adaptations, the necessity for targeted professional development with appropriate resources, and the importance of fostering comprehensive genetic literacy across the entire school community to build capacity among students, staff, and families. These findings have widespread implications for supporting teachers to develop genetic literacy in students with intellectual disability. A key recommendation is to create professional learning and a suite of accessible, multimodal, online resources for students with intellectual disability, their teachers, and the broader school community.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247149","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":"Biallelic SH2B3 germline variants are associated with a neonatal myeloproliferative disease and multisystemic involvement","authors":"Davide Leardini,&nbsp;Elisabetta Flex,&nbsp;Elliot Stieglitz,&nbsp;Sara Cerasi,&nbsp;Salvatore Nicola Bertuccio,&nbsp;Francesco Baccelli,&nbsp;Krisztián Kállay,&nbsp;Paula Kjollerstrom,&nbsp;Sara Batalha,&nbsp;Giovanna Carpentieri,&nbsp;Lucia Pedace,&nbsp;Andrea Ciolfi,&nbsp;Mahmoud Hammad,&nbsp;Maria Miranda,&nbsp;Marta Rojas,&nbsp;Anupama Rao,&nbsp;Andrew J. Innes,&nbsp;Martina Rudelius,&nbsp;Valeria Santini,&nbsp;Marco Raddi,&nbsp;Kok-Hoi Teh,&nbsp;Rita De Vito,&nbsp;Ayami Yoshimi,&nbsp;Marco Tartaglia,&nbsp;Franco Locatelli,&nbsp;Charlotte M. Niemeyer,&nbsp;Riccardo Masetti","doi":"10.1038/s41431-025-01877-y","DOIUrl":"10.1038/s41431-025-01877-y","url":null,"abstract":"Known genetic disorders, such as Noonan syndrome and Down syndrome, can present in the neonatal period or early infancy with myeloproliferative disease (MPD) or abnormal myelopoiesis, which often self-resolves. This phenomenon results from an imbalance in differentiation and cell regulation caused by the genetic condition during perinatal hematopoiesis. Recently, SH2B3 variants have also been associated with neonatal MPD. However, data on their clinical significance, particularly across the spectrum of extra-hematological manifestations, of SH2B3 variants remain limited. Here, we describe the clinical features of ten children with SH2B3-associated disease, arising from germline biallelic SH2B3 loss-of-function (LoF) mutations in eight patients and in two patients from monoallelic germline LoF variants with loss-of-heterozygosity in hematopoietic cells. Patients displayed a MPD in the first weeks of life, which was mostly self-limiting. Following the normalization of blood counts, thrombocytosis developed during childhood. Moreover, they presented with a multisystemic clinical features consisting in delayed growth, variable neurological impairment, autoimmune disorders. These data contribute to the definition of a clinical phenotype associated with germline biallelic SH2B3 LoF variants presenting with neonatal MPD, with important implications for patient management and follow-up.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1127-1135"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01877-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel heterozygous pathogenic variant in HEY2 led to a familial form of non-syndromic Tetralogy of Fallot","authors":"Camille Bergès,&nbsp;Fanny Laffargue,&nbsp;Claire Dauphin,&nbsp;Alex-Vincent Postma,&nbsp;Jean-Benoit Thambo,&nbsp;Caroline Rooryck","doi":"10.1038/s41431-025-01880-3","DOIUrl":"10.1038/s41431-025-01880-3","url":null,"abstract":"Tetralogy of Fallot (TOF) aetiologies remain largely unknown. Although syndromes with genetic cause have been involved, non-syndromic TOF are not completely elucidated, with a genetic diagnosis in less than 20% of the cases. HEY2 is a basic helix-loop-helix (bHLH) repressive transcription factor implicated in cardiac development. In this study, we identify a novel heterozygous missense variant in HEY2 gene segregating within a family presenting with non-syndromic TOF with autosomal dominant transmission. The identified variation c.171 G &gt; C p.(Glu57Asp) was tested through gene reporter assay, revealing a complete disruption of HEY2 repressive activity. These results suggest that HEY2 is a novel gene implicated in the pathogenesis of Tetralogy of Fallot, expanding the genetic spectrum of this congenital heart defect and reinforcing the role of monogenic contributions in non-syndromic TOF.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 8","pages":"1072-1075"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247147","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":"First report of successful pregnancies after treatment with alpelisib for PIK3CA-related overgrowth spectrum","authors":"Gabriel Morin,&nbsp;Antoine Fraissenon,&nbsp;Caroline Chopinet,&nbsp;Estelle Balducci,&nbsp;Sophie Kaltenbach,&nbsp;Patrick Villarese,&nbsp;Vahid Asnafi,&nbsp;Laurent Guibaud,&nbsp;Guillaume Canaud","doi":"10.1038/s41431-025-01885-y","DOIUrl":"10.1038/s41431-025-01885-y","url":null,"abstract":"Alpelisib is a selective PI3Kα inhibitor approved for treating PIK3CA-related overgrowth spectrum (PROS), a group of rare malformation disorders. Given that PI3Kα is a ubiquitous protein involved in cell proliferation, understanding the long-term impact of alpelisib on fertility is of critical importance. Here, we report the favorable outcomes of three pregnancies in PROS patients after prolonged treatment with alpelisib. Although disease progression was observed in all three patients during pregnancy, vascular malformations remained sensitive to alpelisib without evidence of secondary resistance upon resuming treatment. In conclusion, we provide the first evidence that alpelisib does not appear to affect fertility in female patients with PROS.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 8","pages":"1066-1071"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01885-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-based diagnostic studies in genetics: Review and guidance from a multidisciplinary French network","authors":"Marie-Pierre Buisine,&nbsp;Christine Bellanne-Chantelot,&nbsp;Nadège Calmels,&nbsp;Christel Vaché,&nbsp;Thomas Besnard,&nbsp;Benjamin Cogne,&nbsp;Antonio Vitobello,&nbsp;Amélie Piton,&nbsp;Alexandra Martins,&nbsp;Pascaline Gaildrat,&nbsp;Claire-Marie Dhaenens,&nbsp;Svetlana Gorokhova,&nbsp;Nadia Boutry-Kryza,&nbsp;Sandrine Caputo,&nbsp;Raphaël Leman,&nbsp;Sophie Krieger,&nbsp;Gérald Le Gac,&nbsp;Claude Houdayer","doi":"10.1038/s41431-025-01881-2","DOIUrl":"10.1038/s41431-025-01881-2","url":null,"abstract":"The widespread use of high-throughput sequencing for genetic diagnosis has led to considerable advances in patient care, but interpretation of the variants identified remains a challenge and geneticists routinely face the question of variants of uncertain significance. The clinical interpretation of genomic variants requires a high level of expertise to ensure appropriate genetic counseling. Assessing the impact of variants on splicing is a key issue in order to determine their pathogenicity as each variant can impact pre-mRNA splicing by disruption of the splicing code. It is for this reason that a diverse group of French molecular and clinical genetics experts from different diagnostic laboratories nationwide was established to discuss splicing issues and elaborate diagnostic recommendations. We describe an update of these recommendations with the aim of highlighting the importance of transcript characterization for variant interpretation and facilitating the diagnostic implementation of transcript studies, an important source of new diagnostics in human genetics.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 10","pages":"1219-1227"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01881-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic tests as prophecy: understanding self-defeating and self-fulfilling mechanisms in (predictive) genetic testing","authors":"Mayli Mertens,&nbsp;Angus Clarke","doi":"10.1038/s41431-025-01874-1","DOIUrl":"10.1038/s41431-025-01874-1","url":null,"abstract":"Predictive genetic tests are reflexive in that they have the potential not merely to indicate plausible future health outcomes, but to influence the eventual outcome. This article offers an overview of how genetic tests can be self-fulfilling, self-defeating, or otherwise influence what happens to the person’s health. Certain reflexivity is in fact the primary goal of testing, as when those at risk of inherited cancers intend to use this knowledge to decrease said risk. Our analysis emphasises unintended, poorly understood, and often overlooked, reflexive effects of predictive genetic testing, as these may become increasingly important in genetic counselling. First, there is reflexivity in predictive testing for Mendelian, ‘monogenic’ disorders. Second, other reflexive mechanisms reveal the potential for feedback loops between genetic susceptibility and expectations held by the self or others—which are even greater, and more complex, in the context of polygenic susceptibility tests for psychiatric illness and cognitive and behavioural traits. Finally, there are additional implications if these tests are used in prenatal genetic testing. These reflexive effects are increasingly likely as genomic testing is more broadly applied to complex diseases and encouraged by trends in personalised medicine—and especially with direct-to-consumer, commercial genetic testing remaining largely unregulated. Recognising the scope of reflexive predictive effects is already useful in genetic consultation and will become more important as the scope of genomic testing broadens to more complex diseases and non-disease traits. Understanding the underlying mechanisms will furthermore increase the possibility of consciously choosing a beneficial response or effective treatment. Without attention to these effects, the consequences of tests for susceptibility to more complex traits are likely to remain opaque and therefore difficult to evaluate and regulate.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 8","pages":"1051-1056"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01874-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constitutional copy number amplifications: rare or under-evaluated? Revisiting a 25-year-old cold case","authors":"Eliana Salvo,&nbsp;Romano Tenconi,&nbsp;Roberto Giorda,&nbsp;Sara Bertuzzo,&nbsp;Luca Cesana,&nbsp;Roberta Murru,&nbsp;Sabrina Giglio,&nbsp;Mana M. Mehrjouy,&nbsp;Niels Tommerup,&nbsp;Orsetta Zuffardi,&nbsp;Maria Clara Bonaglia","doi":"10.1038/s41431-025-01883-0","DOIUrl":"10.1038/s41431-025-01883-0","url":null,"abstract":"We reanalyzed through a cytogenomics approach a case published 20 years ago, describing a girl with developmental delay and epilepsy. Karyotype and FISH analysis showed a de novo 2.3 Mb terminal inverted-duplication at 8q24.3. The interpretation was inconsistent with the absence of a more distal deletion as expected for distal inverted duplications, and it was inconceivable to highlight rearrangements smaller than 5–10 Mb at that time. Chromosomal microarray (CMA), optical genome mapping (OGM), and short-read whole genome sequencing (srWGS) identified a complex configuration at 8q24.3, which resembles events like chromoanasynthesis or DUP-TRP/INV-DUP (duplication-triplication/inverted-duplication), both characterized by clustered duplications and triplications, some of which are inverted. In the EBV-line genes located in the amplified regions were overexpressed. Despite a more precise definition of the imbalance, we were unable to provide a clear-cut explanation for the proband’s clinical features.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 9","pages":"1212-1216"},"PeriodicalIF":4.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41431-025-01883-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel HSPB8 mutations in severe early-onset myopathy with involvement of respiratory and cardiac muscles cause proteostasis defects in cell models","authors":"Barbara Tedesco,&nbsp;Stojan Peric,&nbsp;Goknur Selen Kocak,&nbsp;Jiayan Tan,&nbsp;Han Duong,&nbsp;Ana Töpf,&nbsp;Vidosava Rakocevic-Stojanovic,&nbsp;Sanja Milenkovic,&nbsp;Yolande Parkhurst,&nbsp;Liliane Gibbs,&nbsp;Angela Martin-Rios,&nbsp;Pier D. Lambiase,&nbsp;Oliver P. Guttmann,&nbsp;Chiara Marini-Bettolo,&nbsp;Elizabeth Harris,&nbsp;Matthew B. Harms,&nbsp;Vukan Ivanovic,&nbsp;Veronica Marchesi,&nbsp;Margherita Milone,&nbsp;Vincent Timmerman,&nbsp;Volker Straub,&nbsp;Angelo Poletti,&nbsp;Virginia Kimonis","doi":"10.1038/s41431-025-01868-z","DOIUrl":"10.1038/s41431-025-01868-z","url":null,"abstract":"Heat shock protein family B (small) member 8 (HSPB8) promotes chaperone-assisted selective autophagy (CASA), which assures proteostasis in muscles and neurons. HSPB8 frameshift mutations found in neuromyopathies are translated on the same frame, generating the same C-terminal extension, which causes HSPB8 aggregation and proteostasis defects. Here, we describe three novel HSPB8 frameshift variants, translated to protein using the third alternative frame to stop codons downstream to the canonical one and to the one used by other known HSPB8 frameshift mutants. Therefore, these variants are predicted to encode a C-terminal extension that is different in length and amino acids. HSPB8 c.562delC and c.520_523delTACT were identified in two unrelated sporadic patients, while c.515delC, in a familial case of early-onset myopathy. Patients may differentially exhibit additional pathological features, such as neuropathy, respiratory insufficiency, and, remarkably, severe cardiomyopathy. Skeletal muscle biopsies revealed variations in fiber size, atrophy, multiple vacuoles, fat infiltration, and eosinophilic inclusions. In&nbsp;a reconstituted cell model of disease the expression of one representative novel HSPB8 mutant results in i) aggregation of the HSPB8 mutant, ii) sequestration of both the HSPB8 wild-type and CASA complex members, as well as iii) the autophagy receptor sequestosome-1 (SQSTM1/p62), iv) accumulation of ubiquitinated substrates, and v) defects in CASA-mediated degradation. Our results prove that the last exon of the HSPB8 gene is highly&nbsp;susceptible to pathogenic mutations, resulting in a wider phenotypic spectrum associated with HSPB8 frameshift variants. Our studies suggest the importance of HSPB8 genetic testing not only for neuropathy and myopathy but also for cardiomyopathy.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"33 8","pages":"1015-1024"},"PeriodicalIF":4.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-025-01868-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An application of the MR-Horse method to reduce selection bias in genome-wide association studies of disease progression.","authors":"Killian Donovan, Jason Torres, Doreen Zhu, William G Herrington, Natalie Staplin","doi":"10.1038/s41431-025-01845-6","DOIUrl":"https://doi.org/10.1038/s41431-025-01845-6","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) of disease progression are vulnerable to collider bias caused by selection of participants with disease at study entry. This bias introduces spurious associations between disease progression and genetic variants that are truly only associated with disease incidence. Methods of statistical adjustment to reduce this bias have been published, but rely on assumptions regarding the genetic correlation of disease incidence and disease progression which are likely to be violated in many human diseases. MR-Horse is a recently published Bayesian method to estimate the parameters of a general model of genetic pleiotropy in the setting of Mendelian Randomisation. We adapted this method to provide bias-reduced GWAS estimates of associations with disease progression, robust to the genetic correlation of disease incidence and disease progression and robust to the presence of pleiotropic variants with effects on both incidence and progression. We applied this adapted method to simulated GWAS of disease incidence and progression with pleiotropic variants and varying degrees of genetic correlation. When significant genetic correlation was present, the MR-Horse method produced less biased estimates than unadjusted analyses or analyses adjusted using other existing methods. Type 1 error rates with the MR-Horse method were consistently below the nominal 5% level, at the expense of a modest reduction in power. We then applied this method to summary statistics from the CKDGen consortium GWAS of kidney function decline. MR-Horse attenuated the effects of variants with known likely biased effects in the CKDGen GWAS, whilst preserving effects at loci with likely true effects.</p>","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215363","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}