Elena Fernández-Suárez, María González-Del Pozo, Cristina Méndez-Vidal, Marta Martín-Sánchez, Marcela Mena, Alejandro García-Nuñez, Nereida Bravo-Gil, María José Morillo-Sánchez, Enrique Rodríguez-de la Rúa, Salud Borrego, Guillermo Antiñolo
{"title":"New genetic diagnoses for inherited retinal dystrophies by integrating splicing tools into NGS pipelines.","authors":"Elena Fernández-Suárez, María González-Del Pozo, Cristina Méndez-Vidal, Marta Martín-Sánchez, Marcela Mena, Alejandro García-Nuñez, Nereida Bravo-Gil, María José Morillo-Sánchez, Enrique Rodríguez-de la Rúa, Salud Borrego, Guillermo Antiñolo","doi":"10.1038/s41525-025-00500-9","DOIUrl":"10.1038/s41525-025-00500-9","url":null,"abstract":"<p><p>Variants affecting pre-mRNA splicing mechanisms are responsible for multiple monogenic disorders. However, their prioritization and interpretation remain challenging. Herein, we designed a strategy for the identification of likely spliceogenic variants in unsolved inherited retinal dystrophy (IRD) cases. We benchmarked thirteen splicing predictors on a curated training dataset, which revealed that the combination of SpliceAI and MaxEnt tools exhibited the best performance for the analysis of most splicing variants. However, for branch point variants, the BranchPoint tool (Alamut®-Batch) was the optimal choice. The proposed combination of tools was assessed using a validation cohort comprising 116 genetically diagnosed individuals with rare diseases, and subsequently applied for the analysis of 211 unsolved IRD families. The pipeline identified 30 likely pathogenic variants, 17 of which were predicted to alter splicing mechanisms. These results demonstrate an increase in diagnostic yield of up to 6.2%, reinforcing the importance of reanalysis strategies focused on identifying spliceogenic variants.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"52"},"PeriodicalIF":4.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical TP53 genetic testing is recommended for HER2-positive breast cancer patients aged 35 or younger.","authors":"Jing Li, Lili Chen, Xuhui Chen, Meng Huang, Wenhui Guo, Minyan Chen, Yuxiang Lin, Yali Wang, Weifeng Cai, Yibin Qiu, Peng He, Qindong Cai, Chuan Wang, Fangmeng Fu","doi":"10.1038/s41525-025-00496-2","DOIUrl":"10.1038/s41525-025-00496-2","url":null,"abstract":"<p><p>Limited information is available for TP53 pathogenic variants (PVs) in early-onset breast cancer patients in China. We investigated the prevalence and clinical relevance of TP53 PVs among 1492 BRCA1/2-negative early-onset breast cancer patients. Peripheral blood samples were collected for TP53 genetic testing through next-generation sequencing. Finally, TP53 PVs were identified in 7 patients (0.47%). The variants p.R248P, p.I251F, and p.G266R were identified for the first time in germline mutations. TP53 carriers exhibited significantly younger diagnosis age (p = 0.003) and higher prevalence of HER2-positive disease (p = 0.020). All carriers were diagnosed before age 35. In HER2-positive patients ≤35 years, the prevalence of TP53 PVs was 2.3%, significantly higher than others after adjusting for a family history of breast cancer and/or ovarian cancer and a personal history of bilateral breast cancer (OR = 13.57, p = 0.002). These results support TP53 genetic testing prioritization for HER2-positive patients under 35 years to guide clinical management, while validation in diverse populations remains essential.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"53"},"PeriodicalIF":4.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huayun Hou, Kyoko E Yuki, Gregory Costain, Anna Szuto, Sierra Barnes, Arun K Ramani, Alper Celik, Michael Braga, Meagan Gloven-Brown, Dimitri J Stavropoulos, Sarah Bowdin, Ronald D Cohn, Roberto Mendoza-Londono, Stephen W Scherer, Michael Brudno, Christian R Marshall, M Stephen Meyn, Adam Shlien, James J Dowling, Michael D Wilson, Lianna Kyriakopoulou
{"title":"Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing.","authors":"Huayun Hou, Kyoko E Yuki, Gregory Costain, Anna Szuto, Sierra Barnes, Arun K Ramani, Alper Celik, Michael Braga, Meagan Gloven-Brown, Dimitri J Stavropoulos, Sarah Bowdin, Ronald D Cohn, Roberto Mendoza-Londono, Stephen W Scherer, Michael Brudno, Christian R Marshall, M Stephen Meyn, Adam Shlien, James J Dowling, Michael D Wilson, Lianna Kyriakopoulou","doi":"10.1038/s41525-025-00505-4","DOIUrl":"10.1038/s41525-025-00505-4","url":null,"abstract":"<p><p>Despite advances in genome sequencing, many individuals with rare genetic disorders remain undiagnosed. Transcriptional profiling via RNA-seq can reveal functional impacts of DNA variants and improve diagnosis. We assessed blood-derived RNA-seq in the largely undiagnosed SickKids Genome Clinic cohort (n = 134), which has been subjected to multiple analyses benchmarking the utility of genome sequencing. Our RNA-centric analysis identifies gene expression outliers, aberrant splicing, and allele-specific expression. In one-third of diagnosed individuals (20/61), RNA-seq reinforced DNA-based findings. In 2/61 cases, RNA-seq revised diagnoses (EPG5 to LZTR1 in an individual with a Noonan syndrome-like disorder) and discovered an additional relevant gene (CEP120 in addition to SON in an individual with ZTTK syndrome). Additionally, ~7% (5/73) of undiagnosed cases had at least one plausible candidate gene identified. This study highlights both the benefits and limitations of whole-blood RNA profiling in refining genetic diagnoses and uncovering novel disease mechanisms.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"51"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabelle A Lucas Beckett, Kate R Emery, Josiah T Wagner, Kathleen Jade, Benjamin A Cosgrove, John Welle, J B Rinaldi, Lindsay Dickey, Kyle Jones, Nick Wagner, Eric M Shull, Jon Clemens, Kalliopi Trachana, Lance Anderson, Allison Kudla, Brett Smith, Hakon Verespej, Li Chi Yuan, Elizabeth Denne, Erica Ramos, Jennifer C Lovejoy, Krzysztof Olszewski, Martin G Reese, Misty J Reynolds, Mandy M Miller, Alexa K Dowdell, Brianna Beck, James M Scanlan, Mary B Campbell, Andrew T Magis, Keri Vartanian, Brian D Piening, Carlo B Bifulco, Ora K Gordon
{"title":"Geno4ME Study: implementation of whole genome sequencing for population screening in a large healthcare system.","authors":"Isabelle A Lucas Beckett, Kate R Emery, Josiah T Wagner, Kathleen Jade, Benjamin A Cosgrove, John Welle, J B Rinaldi, Lindsay Dickey, Kyle Jones, Nick Wagner, Eric M Shull, Jon Clemens, Kalliopi Trachana, Lance Anderson, Allison Kudla, Brett Smith, Hakon Verespej, Li Chi Yuan, Elizabeth Denne, Erica Ramos, Jennifer C Lovejoy, Krzysztof Olszewski, Martin G Reese, Misty J Reynolds, Mandy M Miller, Alexa K Dowdell, Brianna Beck, James M Scanlan, Mary B Campbell, Andrew T Magis, Keri Vartanian, Brian D Piening, Carlo B Bifulco, Ora K Gordon","doi":"10.1038/s41525-025-00508-1","DOIUrl":"10.1038/s41525-025-00508-1","url":null,"abstract":"<p><p>The Genomic Medicine for Everyone (Geno4ME) study was established across the seven-state Providence Health system to enable genomics research and genome-guided care across patients' lifetimes. We included multi-lingual outreach to underrepresented groups, a novel electronic informed consent and education platform, and whole genome sequencing with clinical return of results and electronic health record integration for 78 hereditary disease genes and four pharmacogenes. Whole genome sequences were banked for research and variant reanalysis. The program provided genetic counseling, pharmacist support, and guideline-based clinical recommendations for patients and their providers. Over 30,800 potential participants were initially contacted, with 2716 consenting and 2017 having results returned (47.5% racial and ethnic minority individuals). Overall, 432 (21.4%) had test results with one or more management recommendations related to hereditary disease(s) and/or pharmacogenomics. We propose Geno4ME as a framework to integrate population health genomics into routine healthcare.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"50"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alba Hernangomez-Laderas, Ariadna Cilleros-Portet, Sergi Marí, Bárbara P González-García, Ane Arregi, Alba Jimeno-Romero, Amaia Irizar, Iraia García-Santisteban, Corina Lesseur, Nora Fernandez-Jimenez, Jose Ramon Bilbao
{"title":"Saliva as a potential diagnostic medium: DNA methylation biomarkers for disorders beyond the oral cavity.","authors":"Alba Hernangomez-Laderas, Ariadna Cilleros-Portet, Sergi Marí, Bárbara P González-García, Ane Arregi, Alba Jimeno-Romero, Amaia Irizar, Iraia García-Santisteban, Corina Lesseur, Nora Fernandez-Jimenez, Jose Ramon Bilbao","doi":"10.1038/s41525-025-00509-0","DOIUrl":"10.1038/s41525-025-00509-0","url":null,"abstract":"<p><p>Saliva is an accessible biofluid with potential for non-invasive disease diagnostics. This study explores how genetic susceptibility to common diseases is reflected in DNA methylation (DNAm) and gene expression profiles in saliva. We constructed cis-mQTL (n = 345) and cis-eQTL (n = 277) datasets and examined correlations between DNAm and gene expression. Saliva QTLs were integrated with summary statistics from 36 genome-wide association studies (GWAS) using Summary-based Mendelian Randomization (SMR) to identify disease-associated molecular traits. We found 501 CpG sites and 24 genes as candidate biomarkers, as well as 56 eQTMs linked to conditions such as prostate cancer, squamous cell carcinoma, coronary artery disease, type 2 diabetes, and Parkinson's disease. This work introduces a publicly available resource and suggests that saliva-based molecular signatures may capture systemic disease risk, supporting future exploration as diagnostic markers.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"49"},"PeriodicalIF":4.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khang Ma, Hosei Nakajima, Nipa Basak, Arko Barman, Rinki Ratnapriya
{"title":"Integrating explainable machine learning and transcriptomics data reveals cell-type specific immune signatures underlying macular degeneration.","authors":"Khang Ma, Hosei Nakajima, Nipa Basak, Arko Barman, Rinki Ratnapriya","doi":"10.1038/s41525-025-00507-2","DOIUrl":"10.1038/s41525-025-00507-2","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70-0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where several ML genes exhibited differential expression. Finally, the integration of AMD-GWAS data identified a regulatory variant, rs4133124 at PLCG2, as a novel AMD association. Collectively, our study provides molecular insights into the recurring theme of immune dysfunction in AMD and highlights the significance of glial cell differences in AMD progression.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"48"},"PeriodicalIF":4.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bennet Peterson, Edwin F Juarez, Barry Moore, Edgar Javier Hernandez, Erwin Frise, Jianrong Li, Yves Lussier, Martin Tristani-Firouzi, Martin G Reese, Sabrina Malone Jenkins, Stephen F Kingsmore, Matthew N Bainbridge, Mark Yandell
{"title":"MPSE identifies newborns for whole genome sequencing within 48 h of NICU admission.","authors":"Bennet Peterson, Edwin F Juarez, Barry Moore, Edgar Javier Hernandez, Erwin Frise, Jianrong Li, Yves Lussier, Martin Tristani-Firouzi, Martin G Reese, Sabrina Malone Jenkins, Stephen F Kingsmore, Matthew N Bainbridge, Mark Yandell","doi":"10.1038/s41525-025-00506-3","DOIUrl":"10.1038/s41525-025-00506-3","url":null,"abstract":"<p><p>Identifying critically ill newborns who will benefit from whole genome sequencing (WGS) is difficult and time-consuming due to complex eligibility criteria and evolving clinical features. The Mendelian Phenotype Search Engine (MPSE) automates the prioritization of neonatal intensive care unit (NICU) patients for WGS. Using clinical data from 2885 NICU patients, we evaluated the utility of different machine learning (ML) classifiers, clinical natural language processing (CNLP) tools, and types of Electronic Health Record (EHR) data to identify sick newborns with genetic diseases. Our results show that MPSE can identify children most likely to benefit from WGS within the first 48 h after NICU admission, a critical window for maximally impactful care. Moreover, MPSE provided stable, robust means to identify these children using many combinations of classifiers, CNLP tools, and input data types-meaning MPSE can be used by diverse health systems despite differences in EHR contents and IT support.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"47"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelvin César de Andrade, Emilia M Pinto, Tianna Zhao, Logan P Zeigler, Jung Kim, Neelam Giri, Jeremy S Haley, Lisa J McReynolds, Oscar Florez-Vargas, Aaron H Phillips, Richard W Kriwacki, Sherifa A Akinniyi, Scott B Cohen, Matthew R Emerson, Diane T Smelser, Gretchen M Urban, Cintia Fridman, Gerard P Zambetti, Tracy M Bryan, David J Carey, Christine Kim Garcia, Douglas R Stewart, Sharon A Savage
{"title":"TERT c.3150 G > C (p.K1050N): a founder Ashkenazi Jewish variant associated with telomere biology disorders.","authors":"Kelvin César de Andrade, Emilia M Pinto, Tianna Zhao, Logan P Zeigler, Jung Kim, Neelam Giri, Jeremy S Haley, Lisa J McReynolds, Oscar Florez-Vargas, Aaron H Phillips, Richard W Kriwacki, Sherifa A Akinniyi, Scott B Cohen, Matthew R Emerson, Diane T Smelser, Gretchen M Urban, Cintia Fridman, Gerard P Zambetti, Tracy M Bryan, David J Carey, Christine Kim Garcia, Douglas R Stewart, Sharon A Savage","doi":"10.1038/s41525-025-00501-8","DOIUrl":"10.1038/s41525-025-00501-8","url":null,"abstract":"<p><p>Pathogenic germline variants in telomerase (TERT) cause telomere biology disorders (TBDs) and are associated with bone marrow failure, pulmonary fibrosis, and other complications. TERT c.3150 G > C (p.K1050N) is frequent in the Ashkenazi Jewish (ASH) population and has been identified in ASH families with TBDs. Whole-genome sequencing of 96 p.K1050N heterozygotes from the UK Biobank and All of Us databases revealed a shared haplotype block, supporting a founder effect. Analyses of 15 additional p.K1050N cases validated this haplotype and identified mitochondrial and Y-STR haplogroups consistent with ASH ancestry. Clinical assessments showed that p.K1050N contributes to TBD phenotypes and shortened telomeres, while population data suggest incomplete penetrance. p.K1050N reduces telomerase activity and processivity, and decreases PCNA expression and BrdU incorporation, impairing cell proliferation. Our findings establish TERT p.K1050N as an ASH founder variant associated with TBDs, underscoring the need for genetic screening and long-term clinical studies.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"46"},"PeriodicalIF":4.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laurenz De Cock, Erika D'haenens, Lies Vantomme, Lynn Backers, Aude Beyens, Kathleen Bm Claes, Griet De Clercq, Robin de Putter, Candy Kumps, Nika Schuermans, Jo Sourbron, Hannes Syryn, Simon Tavernier, Eva Vanbelleghem, Olivier Vanakker, Bart Vandekerckhove, Tim Van Damme, Bert Callewaert, Annelies Dheedene, Sarah Vergult, Björn Menten
{"title":"Cracking rare disorders: a new minimally invasive RNA-seq protocol.","authors":"Laurenz De Cock, Erika D'haenens, Lies Vantomme, Lynn Backers, Aude Beyens, Kathleen Bm Claes, Griet De Clercq, Robin de Putter, Candy Kumps, Nika Schuermans, Jo Sourbron, Hannes Syryn, Simon Tavernier, Eva Vanbelleghem, Olivier Vanakker, Bart Vandekerckhove, Tim Van Damme, Bert Callewaert, Annelies Dheedene, Sarah Vergult, Björn Menten","doi":"10.1038/s41525-025-00502-7","DOIUrl":"10.1038/s41525-025-00502-7","url":null,"abstract":"<p><p>RNA sequencing (RNA-seq) has become key to complementing exome and genome sequencing for variant interpretation. We present a minimally invasive RNA-seq protocol using short-term cultured peripheral blood mononuclear cells (PBMCs) with and without cycloheximide treatment, enabling detection of transcripts subject to nonsense-mediated decay. While broadly applicable, this protocol is particularly suited for neurodevelopmental disorders, as up to 80% of the genes in our intellectual disability and epilepsy gene panel are expressed in PBMCs. Applied to 46 affected individuals and 15 parents, RNA-seq revealed splicing defects in six of nine individuals with splice variants, allowing reclassification of seven variants. Targeted cDNA analysis confirmed aberrant splicing in four individuals but missed intron retention in two. Global analyses (FRASER, OUTRIDER, and monoallelic expression) supported findings but did not yield new diagnoses. We propose a flowchart integrating RNA-seq into diagnostic workflows. Overall, our protocol is easily implementable, captures complex splicing events, and enhances variant classification.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"45"},"PeriodicalIF":4.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyao Wang, Yuzhou Zhang, Haoyu Chen, Xiu Juan Zhang, Riping Zhang, Tsz Kin Ng, Jenson A Tham, Ka Wai Kam, Pancy O S Tam, Alvin L Young, Yingying Wei, Mingzhi Zhang, Chi Pui Pang, Clement C Tham, Jason C Yam, Li Jia Chen
{"title":"Genome-wide association study identified novel loci and gene-environment interaction for refractive error in children.","authors":"Yuyao Wang, Yuzhou Zhang, Haoyu Chen, Xiu Juan Zhang, Riping Zhang, Tsz Kin Ng, Jenson A Tham, Ka Wai Kam, Pancy O S Tam, Alvin L Young, Yingying Wei, Mingzhi Zhang, Chi Pui Pang, Clement C Tham, Jason C Yam, Li Jia Chen","doi":"10.1038/s41525-025-00504-5","DOIUrl":"10.1038/s41525-025-00504-5","url":null,"abstract":"<p><p>To identify novel genetic loci for children refractive error, we performed a meta-analysis of two genome-wide association studies (GWASs) of spherical equivalent (SE) in 1,237 children from the population-based Hong Kong Children Eye Study (HKCES) and the Low Concentration Atropine for Myopia Progression (LAMP) study. Replication was conducted in 4,093 Chinese children and 1,814 Chinese adults. Four lead-SNPs (MIR4275 rs292034, TENM3 rs17074027, LOC101928911 rs6925312 and FAM135B rs4609227) showed genome-wide significant association (P ≤ 5.0 × 10<sup>-8</sup>) with SE. TENM3 had been associated with myopia in adults before, whilst the other three loci, MIR4275, LOC101928911 and FAM135B, were novel. Significant interaction between genetic risk scores (GRS) and near work on SE was also detected (β<sub>interaction</sub> = 0.14, P<sub>interaction</sub> = 0.0003). This study identified novel genetic loci for children refractive error and suggested myopia intervention can be individualized based on the genetic risk of children.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"44"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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