American journal of human genetics最新文献

{"title":"Bi-allelic missense variants in human GPN2 result in Perrault syndrome.","authors":"Thomas B Smith,Rabia Faridi,Leigh A M Demain,Sayaka Inagaki,Yasuko Ishibashi,Huw B Thomas,Inna A Belyantseva,Alessandro Rea,King Lam Lai,Arshia Maqbool,Bushra Rauf,Muhammad Asad Usmani,Alejandro A Schäffer,Robert J Morell,Andrew Green,Sondhya Ghedia,Mathilda Wilding,Robin Hay,Yuliya Sokolova,Gavin P Riordan,Isabelle Schrauwen,Khurram Liaqat,Saima Riazuddin,Zubair M Ahmed,Wade W Chien,Langping He,Amanda McGovern,Helen Byers,Glenda M Beaman,Wasim Ahmad,Suzanne M Leal,Robert W Taylor,Sheikh Riazuddin,Raymond T O'Keefe,Thomas B Friedman,William G Newman","doi":"10.1016/j.ajhg.2026.05.016","DOIUrl":"https://doi.org/10.1016/j.ajhg.2026.05.016","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"14 1","pages":"1578-1581"},"PeriodicalIF":9.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying condition-related cell-cell communication events using supervised tensor analysis.","authors":"Qile Dai, Jingjing Yang, Michael P Epstein","doi":"10.1016/j.ajhg.2026.05.005","DOIUrl":"10.1016/j.ajhg.2026.05.005","url":null,"abstract":"<p><p>Many tools have been developed to infer active cell-cell communication (CCC) events, which are essential for understanding biological processes and diseases. However, existing methods for assessing the relationships between CCC events and biological conditions have at least one practical limitation: a lack of clear interpretation, an inability to adjust for confounders, or an inability to model inherent dependencies among CCC events. To comprehensively address these limitations, we introduce STACCato, a supervised tensor analysis tool for identifying condition-related CCC events. STACCato employs a tensor-based regression model to enable statistical inference of the relationships between biological conditions (e.g., disease status or tissue types) and individual CCC events while accounting for confounders and dependencies among CCC events. Through extensive simulations and real-world applications on a lupus single-cell RNA sequencing (scRNA-seq) dataset and an autism single-nucleus RNA-seq (snRNA-seq) dataset, we demonstrate that STACCato consistently provides improved inference of condition-related CCC events compared to alternative methods. The STACCato tool is freely available on GitHub.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1495-1508"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bi-allelic loss-of-function variants in TMEM63B cause syndromic surfactant dysfunction disorder.","authors":"Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol","doi":"10.1016/j.ajhg.2026.05.008","DOIUrl":"10.1016/j.ajhg.2026.05.008","url":null,"abstract":"<p><p>Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen supplementation. Lung histopathology showed alveolar simplification and type II pneumocyte hyperplasia with electron-dense cores in lamellar bodies and interstitial fibrotic changes, findings consistent with impaired surfactant homeostasis. Developmental delay was observed in all individuals, with speech and language development more severely affected. One presented with white matter changes, and another had mild global atrophy on brain imaging. None of the individuals had epilepsy. Identified variants included two splice donor variants, two nonsense variants, and one frameshift variant, all of which were absent or extremely rare in population databases and segregated with disease. Functional evaluation of the splice donor and nonsense variants from three families supported a loss-of-function mechanism. The pulmonary phenotype of these individuals closely parallels that of Tmem63b-knockout mice, which exhibit neonatal respiratory failure due to impaired surfactant secretion. Collectively, these findings define an autosomal-recessive TMEM63B-related syndromic surfactant dysfunction disorder and expand the phenotypic spectrum of TMEM63B-associated disease beyond the central nervous system.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1558-1569"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete chromosome 21 centromere sequencing of families with Down syndrome.","authors":"F Kumara Mastrorosa, Alessia Daponte, Luciana de Gennaro, Shu-Cheng Chuang, Jiadong Lin, Yang Sui, David Porubsky, Keisuke K Oshima, Julie Wertz, Allison N Rozanski, William T Harvey, Yanni Wang, Tiffany Y Leung, Daniel D Chan, Weiya He, Jordan Knuth, Gage H Garcia, Marcelo Ayllon, Katherine M Munson, Kendra Hoekzema, Peter M Lansdorp, Claudia Rita Catacchio, Mario Ventura, Stephanie L Sherman, Emily G Allen, Tracie C Rosser, Glennis A Logsdon, Evan E Eichler","doi":"10.1016/j.ajhg.2026.05.010","DOIUrl":"10.1016/j.ajhg.2026.05.010","url":null,"abstract":"<p><p>Down syndrome, the most common form of human intellectual disability, results from nondisjunction and an extra copy of chromosome 21 (chr21), also known as trisomy 21 (T21). Small centromeres have been hypothesized to contribute to its etiology, and studies on mice suggest that larger centromeres are more efficiently transmitted, yet complete sequencing of chr21 centromeres has been particularly challenging due to their repetitive nature and homology to chromosome 13. Using long-read sequencing, we sequenced and assembled the centromeres from eight families with a child with T21 (one parent-child trio, six mother-child duos, and one singleton), all resulting from maternal meiosis I errors. A comparison of all proband chr21 centromeres (n = 24) to those of control individuals (n = 287) shows that small centromeres are not enriched in families with T21 (p value = 0.72), contrary to earlier reports. However, chr21 extreme centromere size asymmetry (>10-fold) was observed for two of them. Mothers from these two families with T21 carry some of the smallest chr21 centromeres (143 and 181 kbp) observed in female individuals to date, exhibiting a ∼10.7- and ∼19.4-fold centromeric α-satellite higher-order repeat array size difference between the maternally inherited homologs, respectively. Phylogenetic reconstruction reveals that human chr21 is particularly prone to such asymmetry, with some of the biggest size differences occurring over the last ∼17,000 years of human evolution.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1381-1398"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide analysis implicates inner ear development in Ménière disease.","authors":"Zhuozheng Shi, Ravi Mandla, Jingjing Li, Xinzhe Li, Zixuan Eleanor Zhang, Sixing Chen, Sandra Lapinska, Alexander O Flynn-Carroll, Bogdan Pasaniuc, Douglas J Epstein, Iain Mathieson","doi":"10.1016/j.ajhg.2026.05.011","DOIUrl":"10.1016/j.ajhg.2026.05.011","url":null,"abstract":"<p><p>Ménière disease (MD) is a chronic inner ear disorder characterized by recurrent vertigo, fluctuating sensorineural hearing loss, and tinnitus, but its etiology remains poorly understood. We performed a genome-wide meta-analysis of 8,969 MD case subjects and 1,962,542 control subjects across five biobanks, identifying five independent genome-wide significant loci and estimating an observed-scale SNP heritability of 7% (SE 0.8%), indicating a modest but significant contribution of common genetic variation to MD risk. The genome-wide significant signals comprise two independent variants at EYA4, two at EYA1, and one near CYP26A1, with odds ratios between 1.1 and 1.25. Associations at two additional loci, LMO4 and ALDH1A2, fell just below the genome-wide significance threshold (5 × 10^-8 <p < 5 × 10^-7). Fine-mapping and integrative functional analyses implicate two convergent biological processes: developmental regulation of the inner ear, involving EYA4, EYA1, and LMO4, and retinoic acid metabolism, with associations near CYP26A1/C1 and ALDH1A2, suggesting disrupted retinoic acid signaling in sensory and fluid-pressure homeostasis. These developmental regulator genes are robustly expressed in fetal and adult human inner ear cell types, supporting a model in which altered developmental programs predispose individuals to adult vestibular and auditory dysfunction. Phenome-wide and genetic correlation analyses further reveal shared genetic architecture between MD and related traits, including vertigo, tinnitus, hearing loss, migraine, and sleep apnea, situating MD within a broader spectrum of sensory and neurological disorders. Collectively, these findings establish a genetic framework for Ménière disease risk and implicate developmental regulators of the inner ear and retinoic acid signaling as key contributing pathways.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1509-1520"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 transparent and generalizable deep-learning framework for genomic ancestry prediction.","authors":"Camille Rochefort-Boulanger,Matthew Scicluna,Raphaël Poujol,Jean-Christophe Grenier,Pierre Luc Carrier,Sébastien Lemieux,Julie G Hussin","doi":"10.1016/j.ajhg.2026.06.003","DOIUrl":"https://doi.org/10.1016/j.ajhg.2026.06.003","url":null,"abstract":"Accurately characterizing genetic ancestry is critical for ensuring reproducibility and fairness in genomic studies and downstream health research. This study aims to address the prediction of ancestry from genetic data using deep learning, with a focus on generalizability across datasets with diverse populations and on explainability to improve model transparency. We adapt the Diet Network, a deep-learning architecture proven to be effective in handling high-dimensional data, to learn population ancestry from single-nucleotide polymorphism (SNP) data using the populational Thousand Genomes Project dataset. Our results highlight the model's ability to generalize to diverse populations in the CARTaGENE, Montreal Heart Institute, and All of Us biobanks and that predictions remain robust to high levels of missing SNPs. We show that, despite the lack of North African populations in the training dataset, the model learns latent representations that reflect meaningful population structure for North African individuals in the biobanks. To improve model transparency, we apply Saliency Maps, DeepLift, GradientShap, and Integrated Gradients attribution techniques and evaluate their performance in identifying SNPs leveraged by the model. Using DeepLift, we show that the model's predictions are driven by population-specific signals consistent with those identified by traditional population-genetics metrics. This work presents a generalizable and interpretable deep-learning framework for genetic-ancestry inference in large-scale biobanks with genetic data. By enabling more widespread genomic ancestry characterization in these cohorts, this study contributes practical tools for integrating genetic data into downstream biomedical applications, supporting more inclusive and equitable healthcare solutions.","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"25 1","pages":"1461-1477"},"PeriodicalIF":9.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo variants in LDB1 are linked to distinct neurodevelopmental phenotypes determined by variant location and differing pathomechanisms.","authors":"Rebecca Fluri, Mireia Coll-Tané, Theresa Brunet, Benjamin Cogne, Solene Conrad, Mathilde Nizon, Francesco Nicita, Lorena Travaglini, Antonio Novelli, Margie Glissmeyer, Amanda Peterson, Jillian G Buchan, Dan Serber, Kolja Meier, Jutta Gärtner, Susann Diegmann, Veronique Pingault, Tania Attie-Bitach, Thomas Courtin, Michael C Schneider, Wing Hung, Inderneel Sahai, Lauren O'Grady, Katharina Steindl, Sarju G Mehta, Christel Depienne, Delphine Heron, Boris Keren, Solveig Heide, Shane McKee, Franco Laccone, Lisa M Dyer, Catherine Melver, Connie Motter, Wendy D Jones, Zoey Trueblood Wilson, Divya Vats, Kristina Huß, Christiane Zweier, Heinrich Sticht, Anne Gregor","doi":"10.1016/j.ajhg.2026.05.012","DOIUrl":"10.1016/j.ajhg.2026.05.012","url":null,"abstract":"<p><p>LDB1 encodes transcriptional regulator protein LIM domain-binding protein 1, which plays an important role in neurogenesis. Few C-terminal likely gene-disrupting (LGD) variants have been reported in the literature in individuals with congenital ventriculomegaly. Through international collaboration, we now assembled a cohort of 16 individuals with de novo variants affecting various regions of LDB1. Eleven variants affect either the whole gene or the N-terminal dimerization domain (including gene deletions, as well as nonsense-mediated mRNA decay (NMD)-sensitive LGD and missense variants), and five variants (missense or NMD-escaping LGD variants) affect only the C terminus of LDB1 containing the LIM interaction domain. All individuals showed variable neurodevelopmental phenotypes, including developmental delay and behavioral anomalies. In line with literature reports, individuals harboring C-terminal variants additionally presented with ventriculomegaly, which suggests a potential genotype-phenotype correlation. In accordance, we found diverging pathomechanisms in vitro: N-terminal missense variants disrupt homodimerization of LDB1, likely leading to a loss of function, while C-terminal variants impair interaction with the essential partner LHX2 in a dominant-negative manner. These findings were confirmed in vivo in Drosophila melanogaster. Toxicity of overexpressed human LDB1 in Drosophila was not observed with N-terminal missense variants but was exacerbated by C-terminal variants. Similarly, phenotypes associated with LDB1/chi loss were rescued by overexpression of wild-type LDB1 but not by LDB1 harboring N-terminal missense variants or by C-terminal variants that even worsened phenotypes. In summary, our findings indicate that de novo variants in LDB1 are linked to two overlapping but distinct neurodevelopmental phenotypes based on variant location and propose two separate pathomechanisms underlying LDB1-related neurodevelopmental disorders.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1543-1557"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-driven RNA phenotyping captures genetically regulated dimensions of the transcriptome.","authors":"Daniel Munro, Alexander Gusev, Abraham A Palmer, Pejman Mohammadi","doi":"10.1016/j.ajhg.2026.06.005","DOIUrl":"10.1016/j.ajhg.2026.06.005","url":null,"abstract":"<p><p>Transcriptomic diversity across individuals arises from multiple modes of RNA regulation-including precursor messenger RNA (pre-mRNA) expression, splicing, degradation, and other processes-and has been widely leveraged to map molecular quantitative trait loci (xQTLs) and interpret genome-wide association study (GWAS) signals. We recently developed a multimodal framework called Pantry that can extend discovery beyond total expression by integrating multiple transcriptomic modalities. However, Pantry and similar tools remain limited by their reliance on complete gene annotations and the statistical complexity of jointly analyzing correlated modalities. Here, we present LaDDR (latent data-driven RNA phenotyping), a mechanism-agnostic framework that generates orthogonal, latent coverage features per gene, enabling xQTL discovery and GWAS integration without requiring complete gene annotations. Applied to the Genotype-Tissue Expression (GTEx) Project, LaDDR identified an average of 95% more independent xQTLs per tissue than the six transcriptional regulation modes implemented in Pantry (\"knowledge-driven\"). Residualizing known modalities prior to LaDDR and combining with knowledge-driven phenotypes increased discovery by an additional 41% per tissue on average while retaining the interpretability of knowledge-driven signals. In a transcriptome-wide association study (TWAS) of 114 complex traits, the use of LaDDR-derived phenotypes uncovered an average of 11,796 unique gene-trait pairs per tissue versus 8,630 from knowledge-driven phenotypes. The newly captured genetic signals exhibit functional and colocalization qualities consistent with known mechanisms, suggesting that LaDDR broadens the detectable landscape of trait-relevant transcriptomic regulation by efficiently recovering regulatory variation missed by current pipelines.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"113 7","pages":"1399-1414"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"This month in The Journal","authors":"Paul W. Hook, Alyson B. Barnes","doi":"10.1016/j.ajhg.2026.06.006","DOIUrl":"https://doi.org/10.1016/j.ajhg.2026.06.006","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"29 22 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DiscoDivas: Leveraging genetic-ancestry continuum information to interpolate PRS for admixed populations.","authors":"Yunfeng Ruan, Rohan Bhukar, Aniruddh Patel, Satoshi Koyama, Leland Hull, Buu Truong, So Mi Cho, Whitney Hornsby, Haoyu Zhang, Nilanjan Chatterjee, Pradeep Natarajan","doi":"10.1016/j.ajhg.2026.05.006","DOIUrl":"10.1016/j.ajhg.2026.05.006","url":null,"abstract":"<p><p>Genome-wide association study (GWAS) summary statistics for training and individual-level cohorts for fine-tuning are essential for constructing predictive polygenic risk score (PRS) models. However, the relatively low representation of admixed populations in both GWAS summary statistics and individual-level datasets hinders the development of PRSs and equitable clinical translation for admixed populations. Prior work indicates that the most informative PRS model for a genetically homogeneous sample varies linearly in an ancestry continuum space. Guided by these observations, we introduce a genetic-distance-assisted PRS combination pipeline for diverse genetic ancestries (DiscoDivas) to interpolate a harmonized PRS for diverse, especially admixed, genetic ancestries. DiscoDivas leverages multiple PRS models fine-tuned within existing samples, which are mostly of single ancestry, and genetic distance. It provides a new approach to generate genetic-ancestry-specific PRSs when a suitably matched individual-level fine-tuning cohort is unavailable or underpowered. DiscoDivas treats genetic ancestry as a continuous variable and does not require shifting across different models when calculating PRSs for different ancestries. We generated PRSs with DiscoDivas and the current conventional method, i.e., fine-tuning multiple GWAS PRSs using the matched or similar genetic-ancestry samples. DiscoDivas generated a harmonized PRS, performing comparable to or better than the conventional approach, with the greatest advantage exhibited in admixed individuals.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":" ","pages":"1448-1460"},"PeriodicalIF":7.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}