HGG Advances最新文献

{"title":"Integrating spatial transcriptomics and snRNA-seq data enhances differential gene expression analysis results of AD-related phenotypes.","authors":"Shizhen Tang, Shihan Liu, Aron S Buchman, David A Bennett, Philip L De Jager, Jingjing Yang, Jian Hu","doi":"10.1016/j.xhgg.2025.100447","DOIUrl":"10.1016/j.xhgg.2025.100447","url":null,"abstract":"<p><p>Spatial transcriptomics (ST) data provide spatially informed gene expression profiles. However, power is limited for spatially informed differential gene expression (DGE) of complex diseases such as Alzheimer disease (AD), due to small sample sizes of ST data. Conversely, single-nucleus RNA sequencing (snRNA-seq) data offer larger sample sizes for cell-type-specific (CTS) analyses but lack spatial information. Here, we integrated ST and snRNA-seq data to enhance the power of spatially informed CTS DGE analysis of AD-related phenotypes. We first utilized the CeLEry tool to infer six cortical layers of ∼1.5 million cells in the snRNA-seq data that were profiled from the dorsolateral prefrontal cortex (DLPFC) tissue of 436 postmortem brains. Then, we conducted cortical layer- and cell-type-specific (LCS) and CTS DGE analyses based on the linear mixed model, for β-amyloid, tangle density, and cognitive decline. We identified 138 LCS significant genes with false discovery rate (FDR) q <0.05, including 103 for β-amyloid, 24 for tangle density, and 25 for cognitive decline. The majority of these LCS significant genes, including known AD risk genes such as APOE, KCNIP3, and CTSD, cannot be detected by CTS analyses. We also identified 2 genes shared across all 3 phenotypes and 10 shared between 2 phenotypes. Gene set enrichment analyses with the LCS DGE results of microglia in cortical layer 6 of β-amyloid identified 12 significant AD-related pathways. In conclusion, incorporating spatial information with snRNA-seq data enhanced the power of spatially informed DGE analyses. These identified LCS significant genes not only help illustrate the pathogenesis of AD but they also provide potential targets for developing therapeutics of AD.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100447"},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019196","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":"Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets.","authors":"Pardis Zamani, Ursula Houessou, Hasanga D Manikpurage, Zhonglin Li, Manel Dahmene, Nathalie Gaudreault, François Dagenais, Marie-Annick Clavel, Philippe Pibarot, Benoit J Arsenault, Patrick Mathieu, Yohan Bossé, Sébastien Thériault","doi":"10.1016/j.xhgg.2025.100448","DOIUrl":"10.1016/j.xhgg.2025.100448","url":null,"abstract":"<p><p>Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to identify aortic valve-specific genes and compared their expression according to disease status and CAVS severity. We identified 100 specific protein-coding genes in the aortic valve compared to 45 other tissues from the Genotype-Tissue Expression (GTEx) project. Among them, 38 were differentially expressed in CAVS. Ten had a gradient of expression between severity levels and were central in a protein-protein interaction network, most of which were involved in extracellular matrix regulation or inflammation. Among the aortic valve-specific genes, four of the corresponding proteins had a significantly different plasma level in individuals with CAVS. These findings represent a robust foundation for the development of specific biomarkers and therapies for CAVS.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100448"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019627","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":"A multi-level gene-diet interaction analysis of fish oil and 14 polyunsaturated fatty acid traits identifies the FADS and GPR12 loci.","authors":"Susan Adanna Ihejirika, Alexandra Huong Chiang, Aryaman Singh, Eunice Stephen, Han Chen, Kaixiong Ye","doi":"10.1016/j.xhgg.2025.100459","DOIUrl":"10.1016/j.xhgg.2025.100459","url":null,"abstract":"<p><p>Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (p < 5 × 10^-8) in the FADS1-FADS2 gene cluster for total omega-3, omega-3%, docosapentaenoic acid (DHA), DHA%, and the omega-6 to omega-3 ratio. Among the interaction signals for omega-3%, the lead SNP, rs35473591 (C>CT, CT allele frequency = 0.34), had a lower association effect size in the FOS-taking group (β = 0.35 for allele C) than that in the group without FOS (β = 0.42). Likewise, the effect sizes of associations between FOS and omega-3% varied across the three genotype groups (β = 0.45, 0.50, and 0.59, respectively, in C/C, C/CT, and CT/CT). Our gene-level aggregate and transcriptome-wide interaction analyses identified significant signals at two loci around FADS1-FADS2 and GPR12. The contribution of genome-wide gene-FOS interactions to phenotypic variance was statistically significant in omega-3-related traits. This systematic gene-FOS GWIS contributes to our understanding of the genetic architecture of circulating PUFAs underlying FOS response and informs personalized dietary recommendations.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100459"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128950","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":"Severe Joubert syndrome in family with homozygous POC1B p.Arg106Pro variant is due to a co-inherited deep-intronic mutation in the neighboring CEP290 gene.","authors":"Christian Betz, Björn Reusch, Thomas Langmann, Sandra Habbig, Bodo B Beck, Hanno J Bolz","doi":"10.1016/j.xhgg.2025.100429","DOIUrl":"10.1016/j.xhgg.2025.100429","url":null,"abstract":"<p><p>\"En bloc\" inheritance of point mutations in adjacent genes has rarely been described. We have previously reported a family with severe, mostly early-lethal Joubert syndrome (JBTS) with early-onset severe retinal dystrophy (EOSRD) and polycystic kidney disease (PKD), which at that time had been attributed to a homozygous pathogenic missense variant, p.Arg106Pro (c.317G>C), in the ciliary POC1B gene. Because this and other POC1B variants were, in subsequent studies, only reported in patients with non-syndromic childhood or early-adult-onset macular dystrophy, we have now reassessed our index patient by long-read high-fidelity (HiFi) whole-genome sequencing (LR-WGS). We identified a homozygous deep-intronic variant, c.2818-657T>G, in CEP290, a JBTS/Meckel syndrome-associated gene on chromosome 12q21, only 1.28 Mb from the N terminus of POC1B. cDNA analysis revealed aberrant splicing with the frame-shifting inclusion of 37 bp from CEP290 intron 25, predicting the loss of CEP290 function. EOSRD and PKD can fully be ascribed to this CEP290 variant, whose effect outshines the \"background\" non-syndromic POC1B retinopathy and co-segregates with the severe syndromic phenotype. Our novel findings in this family no longer justify POC1B as a JBTS gene. This co-inheritance of two ciliopathies, with the clinically decisive variant hidden deep in an intron, exemplifies the importance of WGS for achieving the complete diagnosis in challenging cases.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100429"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765313","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":"Multiple molecular diagnoses identified through genome sequencing in individuals with suspected rare disease.","authors":"Alka Malhotra, Erin Thorpe, Alison J Coffey, Revathi Rajkumar, Josephine Adjeman, Naomi Dianne Naa Adjeley Adjetey, Sharron Aglobitse, Felix Allotey, Todor Arsov, Joyce Ashong, Ebenezer Vincent Badoe, Donald Basel, Yvonne Brew, Chester Brown, Kerri Bosfield, Kari Casas, Mario Cornejo-Olivas, Laura Davis-Keppen, Abbey Freed, Kate Gibson, Parul Jayakar, Marilyn C Jones, Martina Kawome, Aimé Lumaka, Ursula Maier, Prince Makay, Gioconda Manassero, Marilyn Marbell-Wilson, Charles Marcuccilli, Diane Masser-Frye, Julie McCarrier, Hannah-Sharon Mills, Jeny Balazar Montoya, Gerrye Mubungu, Mamy Ngole, Jorge Perez, Eniko Pivnick, Milagros M Duenas-Roque, Hildegard Pena Salguero, Arturo Serize, Marwan Shinawi, Fabio Sirchia, Claudia Soler-Alfonso, Alan Taylor, Lauren Thompson, Gail Vance, Adeline Vanderver, Keith Vaux, Danita Velasco, Samuel Wiafe, Ryan J Taft, Denise L Perry, Akanchha Kesari","doi":"10.1016/j.xhgg.2025.100430","DOIUrl":"10.1016/j.xhgg.2025.100430","url":null,"abstract":"<p><p>Genome sequencing is a powerful and comprehensive test that detects multiple variants of different types. The interrogation of variants across the genome enables the identification of multiple molecular diagnoses (MMDs) in a single individual. In this retrospective study, we describe individuals in whom MMDs were associated with the proband's indication for testing (IFT), secondary findings, or incidental findings. An MMD is considered where at least one of the findings is associated with the primary IFT and all variants are classified as either likely pathogenic or pathogenic. Clinical genome sequencing was performed for all individuals as part of the iHope program at the Illumina Laboratory Services between September 2017 and December 2023. The iHope cohort included 1,846 affected individuals, with 872 (47.2%) found to have at least one likely pathogenic or pathogenic variant associated with the primary IFT. Of these, 81 (9.3%) individuals had multiple clinically significant molecular findings, including 76 individuals with reported variants associated with 2 different conditions, and 5 individuals with more than 2 molecular findings. A total of 32 individuals (3.7%) had at least 2 molecular diagnoses related to the primary IFT, while in 49 (5.6%) individuals, the variant(s) reported for the second condition constituted a secondary or incidental finding. Our study highlights that among individuals with a likely pathogenic or pathogenic finding identified through genome sequencing, 9% have MMDs, which may have been missed with different testing methods. Of note, approximately 60% of the 81 individuals with an MMD had a potentially actionable secondary or incidental finding.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100430"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804350","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":"Interaction between genetic risk and comorbid conditions in endometriosis.","authors":"Isabelle M McGrath, Valentina Rukins, Triin Laisk, Sally Mortlock, Grant W Montgomery","doi":"10.1016/j.xhgg.2025.100456","DOIUrl":"10.1016/j.xhgg.2025.100456","url":null,"abstract":"<p><p>Endometriosis is a complex disease, and many genetic and environmental risk factors contribute to disease risk. The genetic risk of endometriosis has been well characterized in genome-wide association studies. While few physiological risk factors are known, endometriosis is associated with many comorbid disorders. This study examines the interplay between genetic risk factors, comorbid disorders, and endometriosis. Genetic and health record data from the UK Biobank (5,432 cases; 92,344 controls) and Estonian Biobank (3,824 cases; 15,296 controls) was used to estimate the correlation between comorbidity burden, endometriosis and genetic risk, and to estimate the interactive effects between endometriosis polygenic risk score (PRS) and diagnosis of prevalent comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea, irritable bowel syndrome, diverticular disease, and asthma) on endometriosis prevalence. The comorbidity burden was significantly higher in endometriosis cases and was positively correlated with endometriosis PRS in women without endometriosis but negatively correlated in women with endometriosis. The absolute increase in endometriosis prevalence conveyed by the presence of several comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea) was greater in individuals with a high endometriosis PRS compared to a low endometriosis PRS. These findings, consistent across two biobanks, highlight significant interactions between polygenic risk for endometriosis and the diagnosed comorbidities in endometriosis susceptibility that have implications for understanding the underlying mechanisms contributing to disease risk.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100456"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081082","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":"Advancing genetic services in African healthcare: Challenges, opportunities, and strategic insights from a scoping review.","authors":"Karen Kengne Kamga, Pallissa Fonkam Marlyse, Seraphin Nguefack, Ambroise Wonkam","doi":"10.1016/j.xhgg.2025.100439","DOIUrl":"10.1016/j.xhgg.2025.100439","url":null,"abstract":"<p><p>The implementation of genetic medicine services in African healthcare systems is a complex process that presents both challenges and opportunities. The primary objective of this study was to provide evidence-based recommendations to policymakers and healthcare organizations to help ensure the successful integration of genetic services into African healthcare systems. To achieve this goal, we conducted a scoping review of peer-reviewed studies published between 2003 and 2023. The studies were sourced from PubMed, Scopus, and Africa-wide information databases. We based their findings on eight relevant research studies conducted between 2016 and 2023, covering a wide range of genetic topics in six African countries, including Cameroon, Kenya, Nigeria, Rwanda, South Africa, and Tanzania. The studies identified several challenges associated with the implementation of genetic services in African healthcare systems. These challenges include a lack of awareness and education about genetic diseases, barriers to genetic testing, resource limitations, ethical dilemmas, and challenges in follow-up and retention. However, the authors also highlighted opportunities and strategies for successful implementation, emphasizing preventive measures through community engagement, advocacy, and supportive networks. Apart from the potential to improve healthcare outcomes, implementing genetic services in Africa presents opportunities and challenges for healthcare and biotech companies. To address gaps in disease awareness, we recommend that healthcare providers should invest in education, collaborate with local institutions, and utilize digital platforms. Furthermore, businesses should explore innovative, cost-effective genetic testing models and create dialog platforms like online forums to positively impact African health care.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":"6 3","pages":"100439"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054259","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":"Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity.","authors":"Georgia Mies, Noah L Tsao, Alexandre Houy, Sarah E Coupland, Helen Kalirai, Asta Försti, Kari Hemminki, Hauke Thomsen, Marc-Henri Stern, Carol L Shields, Scott M Damrauer, Katheryn G Ewens, Arupa Ganguly, Iain Mathieson","doi":"10.1016/j.xhgg.2025.100465","DOIUrl":"10.1016/j.xhgg.2025.100465","url":null,"abstract":"<p><p>Uveal melanoma (UM) is a rare but frequently metastasizing cancer. Genome-wide association studies have identified three common genome-wide significant germline risk loci. Here, we perform a genome-wide association study on 401 new cases and conduct a meta-analysis with three independent previously published cohorts for a total sample size of 2,426 cases. We confirm the three previously identified risk loci and identify four additional genome-wide significant loci. We find that eye pigmentation-decreasing variants are systematically associated with increased UM risk and that selection for lighter pigmentation in the past 5,000 years explains about 73% of the difference in UM incidence between Northern and Southern Europe. We find evidence of effect size heterogeneity at significant loci across cohorts, in particular, a weaker association between eye pigmentation and UM in a Finnish cohort. Finally, we confirm differential effect sizes between uveal melanoma cases with and without loss of chromosome 3, the major determinant of metastatic risk. Our study identifies novel germline risk factors for UM and highlights genetic and environmental heterogeneity in its etiology.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100465"},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267446","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":"Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4.","authors":"Audrey Winkelsas, Athena Apfel, Brian Johnson, George Harmison, Kimberly Diaz Perez, Dongjun Li, Vivian G Cheung, Christopher Grunseich","doi":"10.1016/j.xhgg.2025.100435","DOIUrl":"10.1016/j.xhgg.2025.100435","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis 4 (ALS4) is an autosomal dominant motor neuron disease that is molecularly characterized by reduced R-loop levels and caused by pathogenic variants in senataxin (SETX). SETX encodes an RNA/DNA helicase that resolves three-stranded nucleic acid structures called R-loops. Currently, there are no disease-modifying therapies available for ALS4. Given that SETX is haplosufficient, removing the product of the mutated allele presents a potential therapeutic strategy. We designed a series of siRNAs to selectively target the RNA transcript from the ALS4 allele containing the c.1166T>C mutation (p.Leu389Ser). Transfection of HEK293 cells with siRNA and plasmids encoding either wild-type or mutant (Leu389Ser) epitope-tagged SETX revealed that three siRNAs specifically reduced mutant SETX protein levels while having minimal effect on the wild-type SETX protein. In ALS4 primary fibroblasts, siRNA treatment silenced the endogenous mutant SETX allele while sparing the wild-type allele and restored R-loop levels in patient cells. Our findings demonstrate that mutant SETX, differing from wild-type by a single nucleotide, can be effectively and specifically silenced by RNA interference.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100435"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812657","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":"Multidisciplinary stakeholder-informed identification of key characteristics for implementation of workplace genetic testing.","authors":"Elizabeth Charnysh, Kunal Sanghavi, Kerry A Ryan, Alyx Vogle, Alexandra Truhlar, Subhamoy Pal, Jonathan M Reader, J Scott Roberts, Charles Lee, Anya E R Prince, W Gregory Feero","doi":"10.1016/j.xhgg.2025.100458","DOIUrl":"10.1016/j.xhgg.2025.100458","url":null,"abstract":"<p><p>Workplace genetic testing (wGT) is an evolving model for genetic testing where employees are offered consumer genetic testing through employer-sponsored wellness programs. However, the potential harms, benefits, and key characteristics for best implementation practices for wGT have yet to be defined. To address this issue, we conducted a three-round modified Delphi process, including multiple rounds of survey and a virtual deliberative workshop, with purposely chosen wGT stakeholders (employees, employers, ethical, legal, and social implications [ELSI] professionals, genetic testing industry representatives, and healthcare professionals) to share their perspectives. From the modified Delphi process, we identified 12 key characteristics for the implementation of wGT that were perceived to increase the potential for benefit while reducing the risk of potential harms. Most participants agreed that privacy/security, voluntariness, transparency, understanding and education, anti-discrimination, employee control, and evidence-based testing measures were both important (>90%) and necessary (>75%) for the implementation of wGT. However, some participants also expressed a lack of confidence in the likelihood of achieving these characteristics in wGT programs. Overall, stakeholders expressed qualified support for wGT at the conclusion of the modified Delphi process. Their perspectives on the topic varied over the course of the process and were at least partially contingent on whether the aforementioned 12 key characteristics were met. These findings help inform the establishment of a normative framework for wGT assessment.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":" ","pages":"100458"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136415","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}