HGG Advances最新文献

{"title":"Whole-genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.","authors":"Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon LeFaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A McCarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott","doi":"10.1016/j.xhgg.2025.100499","DOIUrl":"10.1016/j.xhgg.2025.100499","url":null,"abstract":"<p><p>In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls (∼37X). To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of the association of BD with single variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD genome-wide association study loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole-genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100499"},"PeriodicalIF":3.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.","authors":"Jarosław Dulski, Arun K Boddapati, Barbara Risi, Pablo Iruzubieta, Antonio Orlacchio, Roberto Fernández-Torrón, Tamara Castillo-Triviño, Adolfo López de Munain, Steve Vucic, Alessandro Padovani, Laura Donker Kaat, Tahsin Stefan Barakat, Leonard Petrucelli, Mercedes Prudencio, John E Landers, Jochen H Weishaupt, Andreas Prokop, Massimiliano Filosto, Zbigniew K Wszolek, Devesh C Pant","doi":"10.1016/j.xhgg.2025.100498","DOIUrl":"10.1016/j.xhgg.2025.100498","url":null,"abstract":"<p><p>KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10 and ALS individuals and compare them to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 individuals. Moreover, these findings can now be used to gain mechanistic understanding of axonopathies linking to N- versus C-terminal KIF5A variants affecting both central and peripheral nervous systems.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100498"},"PeriodicalIF":3.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overlap between COPD genetic association results and transcriptional quantitative trait loci.","authors":"Aabida Saferali, Wonji Kim, Robert P Chase, Christopher Vollmers, Edwin K Silverman, Michael H Cho, Peter J Castaldi, Craig P Hersh","doi":"10.1016/j.xhgg.2025.100493","DOIUrl":"10.1016/j.xhgg.2025.100493","url":null,"abstract":"<p><p>Genome-wide association studies (GWASs) have identified multiple genetic loci associated with chronic obstructive pulmonary disease (COPD). Here, we identify SNPs that are associated with alternative splicing (splicing quantitative trait loci [sQTLs]) and gene expression (expression QTLs [eQTLs]) to identify functions for COPD-associated genetic variants. RNA sequencing on whole blood from 3,743 subjects in the COPDGene Study and from lung tissue of 1,241 subjects from the Lung Tissue Research Consortium (LTRC) was analyzed. Associations between all SNPs within 1,000 kb of a gene (cis-) and splice and gene expression quantifications were tested using tensorQTL. We assessed colocalization with COPD-associated SNPs from a published GWAS. After adjustment for multiple statistical testing, we identified 28,110 splice sites corresponding to 3,889 unique genes that were significantly associated with genotype in COPDGene whole blood and 58,258 splice sites corresponding to 10,307 unique genes associated with genotype in LTRC lung tissue. To determine what proportion of COPD-associated SNPs were associated with transcriptional splicing, we performed colocalization analysis between COPD GWAS and sQTL data and found that 38 genomic windows, corresponding to 33 COPD GWAS loci, had evidence of colocalization between QTLs and COPD. The top five colocalizations between COPD and lung sQTLs include Nephronectin (NPNT), F box protein 38 (FBXO38), Hedgehog interacting protein (HHIP), Netrin 4 (NTN4), and Betacellulin (BTC). Overall, a total of 38 COPD GWAS loci contain evidence of sQTLs, suggesting that analysis of sQTLs in whole blood and lung tissue can provide insights into disease mechanisms.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100493"},"PeriodicalIF":3.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of de novo variants in KCTD10 as a proposed cause for multiple congenital anomalies.","authors":"Michelle M Morrow, Erin Torti, Bobbi McGivern, Ryan Gates, Mir Reza Bekheirnia, Nasim Bekheirnia, Leandra Folk, Shannon Holtrop, Timothy Blake Palculict, Olivia L Redlich, Adi Reich, Maria J Guillen Sacoto, Lisong Shi, Ingrid M Wentzensen, Kirsty McWalter","doi":"10.1016/j.xhgg.2025.100426","DOIUrl":"10.1016/j.xhgg.2025.100426","url":null,"abstract":"<p><p>To date, the KCTD10 gene (MIM: 608726) has not been definitively associated with a human disease, although studies in animal models suggest that it plays a role in embryonic development. We have identified multiple unrelated individuals with de novo missense variants and overlapping phenotypes, including congenital heart anomalies and congenital anomalies in other organ systems, in our internal database. This report includes a detailed description of the genotype and phenotype for two consented individuals and aggregate data of additional individuals who were not available for case-specific publication. Based on the data presented here, we propose that damaging de novo missense KCTD10 variants are associated with an autosomal dominant phenotype that includes cardiac and other congenital anomalies. We encourage additional studies to further characterize this condition and identify a mechanism for disease.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100426"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-tissue transcriptome-wide association study identifies novel candidate genes and pleiotropy effects across four abdominal hernia subtypes.","authors":"Dima L Chaar, Chen Jiang, Brandon Cowan, Sahil Patel, Mark Kvale, Jie Yin, Rouzbeh Mostaedi, Nadav Ahituv, Eric Jorgenson, Thomas J Hoffmann, Hélène Choquet","doi":"10.1016/j.xhgg.2025.100436","DOIUrl":"10.1016/j.xhgg.2025.100436","url":null,"abstract":"<p><p>Abdominal hernias are caused by the protrusion of an organ or tissue through a weakened abdominal wall. Genome-wide association studies (GWASs) have identified 81 genetic susceptibility loci for different hernia subtypes, with 26 loci associated with more than one hernia type; however, additional work is needed to prioritize causal genes at known GWAS loci, identify novel ones, and characterize shared genetic effects across hernia subtypes. We conduct transcriptome-wide association study (TWAS) analyses of four hernia subtypes (i.e., inguinal, umbilical, ventral, femoral) using GWAS summary statistics from up to 57,291 hernia cases and 436,717 controls of European ancestry. Our TWAS, which leveraged imputed gene expression from 54 tissues, identifies 211 unique genes, of which 85 did not overlap with known hernia-associated loci. We also investigate patterns of pleiotropy and identify four genes (LYPLAL1-AS1, RIMKLBP2, AL513283.1, and EFEMP1) associated with all four hernia subtypes. Our findings enhance understanding of transcriptomic mechanisms through which hernias develop.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100436"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted sequencing for hereditary breast and ovarian cancer in BRCA1/2-negative families reveals complex genetic architecture and phenocopies.","authors":"Jocelyn N Plowman, Evanjalina J Matoy, Lavanya V Uppala, Samantha B Draves, Cynthia J Watson, Bridget A Sefranek, Mark L Stacey, Samuel P Anderson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Yusi Fu, Holly A F Stessman","doi":"10.1016/j.xhgg.2025.100453","DOIUrl":"10.1016/j.xhgg.2025.100453","url":null,"abstract":"","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100453"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic signatures of rare variant impacts across sex and the X chromosome.","authors":"Rachel A Ungar, Taibo Li, Nikolai G Vetr, Nicole Ersaro, Alexis Battle, Stephen B Montgomery","doi":"10.1016/j.xhgg.2025.100463","DOIUrl":"10.1016/j.xhgg.2025.100463","url":null,"abstract":"<p><p>The human X chromosome contains hundreds of genes and has well-established impacts on sex differences and traits. However, the X chromosome is often excluded from many genetic analyses, limiting broader understanding of variant effects. In particular, the functional impact of rare variants on the X chromosome is understudied. To investigate functional rare variants on the X chromosome, we use observations of outlier gene expression from Genotype Tissue Expression consortium data. We show that outlier genes are enriched for having nearby rare variants on the X chromosome, and this enrichment is stronger for males. Using the RIVER model, we identified 733 rare variants in 450 genes predicted to have functional differences between males and females. We examined the pharmacogenetic implications of these variants and observed that 25% of drugs with a known sex difference in adverse drug reactions were connected to genes that contained a sex-biased rare variant. We further identify that sex-biased rare variants preferentially impact transcription factors with predicted sex-differential binding, such as the XIST-modulated SIX1. Overall, we observed more within-sex variation than between-sex variation. Combined, our study investigates functional rare variants on the X chromosome, and further details how sex stratification of variant effect prediction improves identification of rare variants with predicted sex-biased effects, transcription factor biology, and pharmacogenomic impacts.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100463"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic PPP2R5D variants disrupt neuronal development and neurite outgrowth in patient-derived neurons that are reversed by allele-specific knockdown.","authors":"Randee E Young, Michael V Zuccaro, Charles A LeDuc, Noelle D Germain, Tae Hyun Kim, Patrick Sarmiere, Wendy K Chung","doi":"10.1016/j.xhgg.2025.100450","DOIUrl":"10.1016/j.xhgg.2025.100450","url":null,"abstract":"<p><p>A significant barrier to the treatment of neurodevelopmental disorders (NDDs) is a limited understanding of disease mechanisms. Heterozygous missense variants in PPP2R5D cause Houge-Janssens syndrome 1, a rare NDD characterized by macrocephaly, developmental delay, intellectual disability, seizures, autism spectrum disorder, and early-onset Parkinson disease. This study investigated the impact of pathogenic PPP2R5D variants on neuronal development and evaluated allele-specific knockdown as a potential therapeutic strategy. Induced pluripotent stem cells derived from individuals carrying the E198K and E420K variants, along with CRISPR-corrected isogenic controls, were differentiated into neural progenitors and cortical glutamatergic neurons. Patient-derived neural progenitors were hyper-proliferative, and glutamatergic neurons differentiated from these cells exhibited increased neurite outgrowth. Notably, neuronal overgrowth phenotypes were not observed in neurons lacking PPP2R5D, suggesting the disorder does not result from loss of function. RNA sequencing (RNA-seq) of glutamatergic neurons derived from patient lines compared to their isogenic controls revealed disruptions in pathways critical for neuronal development, synaptic signaling, and axon guidance. To target pathogenic transcripts, antisense oligonucleotides (ASOs) were designed to selectively knock down the E198K allele, the most common disease-causing missense variant. The most effective ASOs reversed neurite outgrowth defects in patient-derived neurons. These findings uncover molecular mechanisms underlying PPP2R5D-related NDDs and support allele-specific knockdown as a potential therapeutic approach.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100450"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of technically challenging variants: Whole-genome sequencing improves diagnostic yield in patients with high clinical suspicion of rare diseases.","authors":"Hau-Yee Ng, Wei Ma, Wai-Kei J Lam, Chak-Sing Lau, Ho-Ming Luk, Lisa W C Au, Shirley S W Cheng, Josephine S C Chong, Stephanie Ho, Becky M Ma, Shirley Y Y Pang, Annie T W Chu, Brian H Y Chung","doi":"10.1016/j.xhgg.2025.100469","DOIUrl":"10.1016/j.xhgg.2025.100469","url":null,"abstract":"<p><p>The total burden of rare diseases is significant worldwide, with over 300 million people being affected. Many rare diseases have both well-defined clinical phenotypes and established genetic causes. However, a remarkable proportion of patients with high clinical suspicion of a rare disease remain genetically undiagnosed and stuck in the diagnostic odyssey after having a cascade of conventional genetic tests. One of the major factors contributing to this is that many types of variants are technically intractable to whole-exome sequencing (WES). In this study, the added diagnostic power of whole-genome sequencing (WGS) for patients with clinically suspected rare diseases was assessed by detecting technically challenging variants. 3,169 patients from the Hong Kong Genome Project (HKGP) were reviewed, identifying 322 individuals having high clinical suspicion of a rare disorder with well-established genetic etiology. Notably, 180 patients have performed at least one previous genetic test. Through PCR-free short-read WGS and a comprehensive in-house analytic pipeline, causative variants were found in 138 patients (138 of 322, 42.9%), 30 of which (30 of 138, 21.7%) are attributed to technically challenging variants. These included 6 variants in low-coverage regions with PCR bias, 2 deep intronic variants, 2 repeat expansions, 19 structural variants, and 2 variants in genes with a homologous pseudogene. The study demonstrated the indispensable diagnostic power of WGS in detecting technically challenging variants and the capability to serve as an all-in-one test for patients with high clinical suspicion of rare diseases.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100469"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of genetic ancestry on survival outcomes in pediatric rhabdomyosarcoma: A report from the Children's Oncology Group.","authors":"Ekene A Onwuka, Christina L Magyar, Bailey A Martin-Giacalone, Michael E Scheurer, Deborah A Marquez-Do, Mark Zobeck, Elizabeth G Atkinson, Erin R Rudzinski, Michael A Arnold, Donald A Barkauskas, David Hall, Javed Khan, Jack F Shern, Paul Scheet, Brian Crompton, Corinne M Linardic, Douglas S Hawkins, Rajkumar Venkatramani, Lisa Mirabello, Chad D Huff, Melissa A Richard, Philip J Lupo","doi":"10.1016/j.xhgg.2025.100466","DOIUrl":"10.1016/j.xhgg.2025.100466","url":null,"abstract":"<p><p>Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; and (2) overall survival (OS), defined as the time from study enrollment to death from any cause. Genetic ancestry was estimated using Grafpop software, and Cox regression assessed the association between genetic ancestry and EFS and OS, considering RMS overall, by fusion status, and by histological subtype. Covariates included sex, age at diagnosis, tumor stage, and histology, except during stratified analyses. In embryonal RMS and PAX3/7:FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.07-3.97, p = 0.03 and HR 2.01, 95% CI 1.07-3.76, p = 0.03, respectively) and OS (HR 2.30, 95% CI 1.09-4.84, p = 0.03 and HR 2.33, 95% CI 1.15-4.70, p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision-medicine-based efforts.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100466"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}