Annals of Human Genetics最新文献

{"title":"The History of the Panmictic Population Concept and Its Legacy in Contemporary Population Genetics","authors":"Andy Walton,&nbsp;Alex Aylward,&nbsp;Mark G. Thomas,&nbsp;Adam Rutherford","doi":"10.1111/ahg.70015","DOIUrl":"10.1111/ahg.70015","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> ABSTRACT</h3>\u0000 \u0000 <p>The panmictic population concept is at the heart of population, evolutionary and conservation genetics. However, in nature, true panmictic populations are vanishingly rare. As an idea conceived for modelling evolutionary dynamics, it has been thought that the assumption of panmixia was formalised during the development of the Modern Synthesis. Here, we show that while the idea's longevity is almost certainly due to its mathematical convenience, it became embedded in evolutionary thought much earlier, initially as a way to reconcile long-standing essentialist ideas with the advent of Darwin's theories. Though the principles of essentialism and reversion have been largely rejected, these ideas persist in shaping assumptions made about populations in contemporary genetics research, including how they are conceptualised and sampled. This legacy has important implications for the interpretation of genomic findings in human evolution, conservation and medicine. From an evaluation of this history and its legacy, we contend that while the panmictic population concept has been, and continues to be useful, with the generation of terabytes of genomic data in the 21st century, its utility is likely to diminish as the need for continuous space models grows.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"274-284"},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the LOXHD1 Mutational Spectrum: A North Indian Case of ARNSHL","authors":"Pratiksha Chheda,&nbsp;Tavisha Dama,&nbsp;Tanmay Deshpande","doi":"10.1111/ahg.70017","DOIUrl":"10.1111/ahg.70017","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 2","pages":"65-66"},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Relationships Between Gastroesophageal Reflux Disease and Myocardial Infarction: Insights From Univariable and Multivariable Mendelian Randomization Analyses","authors":"Xiaoya Zheng,&nbsp;Teng Hu,&nbsp;Tianxiang Fang,&nbsp;Pengpeng Su,&nbsp;Yingsong Wang,&nbsp;Ning Huangfu","doi":"10.1111/ahg.70012","DOIUrl":"10.1111/ahg.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Observational studies have indicated that gastroesophageal reflux disease (GERD) is connected to myocardial infarction (MI). Nonetheless, the question of causality in these relationships remains unresolved, given the potential influence of confounding variables. The aim is to study the causal link of GERD with MI and determine whether MI factors have any mediation effects in the causative chain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GERD (129,080 cases and 473,524 controls) and MI (831,000 individuals) were obtained from the latest genome-wide association study summary-level data. Two-sample Mendelian randomization (MR) analyses were performed to assess the associations of genetically predicted GERD with MI risk. After adjusting for several confounders, multivariable MR was employed to determine the independent impacts of GERD on MI risk. Two-step MR analyses were carried out to investigate the mediating impacts of these modifiable factors in the relationships between GERD and MI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The current univariable MR analysis indicated that GERD was connected to MI (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.48–1.76; <i>p</i> = 1.01 × 10⁻²⁶), whereas this correlation remained after controlling for body mass index, cigarettes per day, and alcohol consumption. Two-step MR found that several MI-associated risk factors mediated the associations between GERD and MI, with hypertension (mediation proportion: 14.4%) and type-2 diabetes mellitus (12.0%) exhibiting higher mediation proportions among the mediating networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies modifiable cardiovascular risk factors that may mediate the GERD-MI association, with hypertension (14.4%) and T2DM (12.0%) identified as the predominant modifiable mediators. These findings highlight the clinical importance of integrated cardiometabolic monitoring in GERD patients, suggesting that targeted management of blood pressure and glycemic control may mitigate MI risk in GERD populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 1","pages":"52-62"},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effectiveness of Forensic Application and Population Genetic Diversity Using a Multi-InDel System in Chinese Hezhou and Southern Shaanxi Han Populations","authors":"Xi Wang,&nbsp;Qiong Lan,&nbsp;Yifeng Lin,&nbsp;Xi Yuan,&nbsp;Shuyan Mei,&nbsp;Fanzhang Lei,&nbsp;Bonan Dong,&nbsp;Ming Zhao,&nbsp;Meiming Cai,&nbsp;Chunmei Shen,&nbsp;Bofeng Zhu","doi":"10.1111/ahg.70001","DOIUrl":"10.1111/ahg.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multi-insertion/deletion (multi-InDel) markers have greater potential in forensic genetics than InDel, and their efficacy in paternity testing, individual identification, DNA mixture detection, and ancestry inference remains to be explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and method</h3>\u0000 \u0000 <p>We designed an efficient and robust system consisting of 41 multi-InDels to evaluate its efficacy in forensic applications in Chinese Hezhou Han (HZH) and Southern Shaanxi Han (SSH) populations and explore the genetic relationships among the SSH, HZH, and 26 reference populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and conclusions</h3>\u0000 \u0000 <p>The obtained results showed that most of the 41 multi-InDels had relatively high genetic variations. The cumulative power of discrimination and probability of exclusion values of 40 multi-InDels (except MI38) in HZH and SSH populations both exceeded 1 − e⁻²⁵ and 1 − e⁻⁶, respectively. The genetic compositions of HZH and SSH populations were similar to those of East Asian populations, and the multi-InDel system could well distinguish East Asians, Africans, and Europeans. These results indicated that the multi-InDel system can serve as an effective tool to provide important clue for the forensic practical application and also to better analyze the genetic background of Chinese Han population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 1","pages":"41-51"},"PeriodicalIF":1.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetics of Acne","authors":"Maurice A. M. Van Steensel","doi":"10.1111/ahg.70014","DOIUrl":"10.1111/ahg.70014","url":null,"abstract":"<p>This review addresses the genetics of acne vulgaris, the most common skin disease. It is characterized by the presence of comedones (blackheads), papules, and pustules. The condition is associated with sebaceous glands in the face and chest, which produce an oily substance called sebum. In developed nations, acne affects over 80% of adolescents. Mild disease usually resolves spontaneously. More severe acne can leave permanent, disfiguring scarring and strongly affects quality of life. In those cases, medical intervention is warranted. To date, antibiotics and retinoids (synthetic vitamin A derivatives) are the mainstays of treatment. Depending on the severity of the condition, these drugs may be administered either topically or systemically.</p><p>Whilst generally effective, they do come with significant drawbacks. Antibiotic use for treating acne is contributing to antimicrobial resistance. In addition, indiscriminate eradication of the skin microbiome negatively impacts skin health. Retinoids are teratogenic and have other undesirable side effects, such as skin irritation and increased UV sensitivity. Thus, there is a clear need for effective interventions that target the underlying disease mechanism, minimizing side effects.</p><p>Rapid progress has recently been made in understanding the mechanisms underlying acne. For decades, it was assumed that blackhead formation results from the accumulation of sebum in the hair follicle opening, due to increased sebum production at the onset of puberty. Subsequent colonization by the commensal bacterium <i>Cutibacterium acnes</i> then was thought to cause inflammation. It was also postulated that this micro-organism could induce blackheads. There are, however, several problems with this supposed sequence of events, not the least of which is that it doesn't explain how retinoids work, or why sebaceous glands associated with blackheads are atrophic and hence produce less sebum, not more.</p><p>Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne. Together with insights from mouse models, this new perspective is transforming the way we think about acne and its treatment.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"333-341"},"PeriodicalIF":1.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited Susceptibility to Cancer: Past, Present and Future","authors":"Shirley V. Hodgson,&nbsp;William D. Foulkes,&nbsp;Eamonn R Maher,&nbsp;Clare Turnbull","doi":"10.1111/ahg.70013","DOIUrl":"10.1111/ahg.70013","url":null,"abstract":"<p>Germline pathogenic variants (GPVs, ‘mutations’) causing inherited susceptibility to certain cancers (cancer susceptibility genes, CSGs) broadly belong to one of two main classes—loss of function variants in tumour suppressor genes (TSGs) or gain of function variants in proto-oncogenes (an over-simplification). Genomic analyses of tumours identify ‘driver mutations’ promoting tumour growth and somatic variants which contribute to ‘mutation signatures’ which, with histopathology, can be used to subclassify cancers with implications for causality and treatment. The identification of susceptible individuals is important, as they and their relatives may be at elevated risk of tumours, and this can influence optimal cancer treatment. Classically, cancer risk assessment utilises family history, lifestyle/environment factors, and any non-neoplastic clinical findings, followed by genetic testing of high/moderate penetrance CSGs. In cancer cases not caused by highly penetrant CSGs, multiple variants conferring relatively small risks play a major role. These were discovered by genome-wide association (GWAS) studies. The utility of polygenic risk scores (PRS) derived from multiple such variants for clinical risk profiling is being assessed. Access to genetic tests is improved by widening eligibility criteria for testing and empowering non-genetic clinicians to identify CSG GPVs and manage carriers. This will contribute to expanding programmes of screening, prevention and early detection (SPED), with personalised surveillance and prophylactic interventions, and exploit knowledge of the molecular mechanisms of cancer susceptibility to develop novel cancer therapies. In some jurisdictions, population testing is being considered, but GPV penetrance in this setting can be unclear, and the public health implications are complex.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"354-365"},"PeriodicalIF":1.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Causal Association Between Follicle-Stimulating Hormone and Alzheimer's Disease: Genetic Loci Study and Mendelian Randomization Study","authors":"Chenchen Ding,&nbsp;Xiaohong Xu,&nbsp;Bangliang Xu,&nbsp;Jiali Wu","doi":"10.1111/ahg.70004","DOIUrl":"10.1111/ahg.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) predominantly affects older women, with research suggesting elevated follicle-stimulating hormone (FSH) levels in postmenopausal women correlate with AD risk and cognitive decline. Understanding the causal relationship between FSH and AD is essential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We selected single-nucleotide polymorphisms (SNPs) linked to FSH as instrumental variables (IVs) for Mendelian randomization (MR). Statistical methods, including inverse variance weighted (IVW), MR Egger, Weighted Median, Weighted Mode, and Simple Mode, were employed to assess causality and potential pleiotropy. Shared genetic loci between FSH and AD were explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We carefully identified and utilized a total of 20 valid SNPs as IVs to assess the potential causal relationship between FSH and AD. Our analysis revealed a significant causal association between genetically determined FSH levels and AD [beta = −0.004; OR = 0.996, 95% confident interval (CI): 0.994–0.999; <i>p</i> = 0.002]. We successfully identified 20 SNPs that correspond to 8 differentially expressed genes (DEGs) between AD and non-demented (ND). These genes have not been previously reported to be linked to either FSH or AD. We conducted an in-depth analysis to explore the potential roles of these genes in the context of FSH and AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our MR study revealed that FSH potentially has a causal association with AD. Additionally, FSH might possess distinctive biological mechanisms that influence the development of AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"90 1","pages":"25-40"},"PeriodicalIF":1.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fortunes of Genomic Medicine: A Quarter Century of Promise","authors":"Steve Sturdy","doi":"10.1111/ahg.70011","DOIUrl":"10.1111/ahg.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The culmination of the Human Genome Project in the early 2000s came wreathed in promises of a revolution in medicine and healthcare. The ensuing quarter century has seen remarkable growth in genomic medicine, as well as notable shifts in the promissory rhetoric that accompanies it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This essay draws on a contextualist close reading of scientific and policy literature published from the 1990s to the present, using thematic and narrative analysis informed by perspectives from the sociology of expectations, to examine the role of different kinds of promissory claims in shaping the development of genomic medicine in the UK, and particularly England, over that period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Early promises about the medical benefits that will follow from the development of genomic medicine have been scaled back and refocused as the possibilities and limitations of genomic technologies have become apparent; while investment has shifted from basic discovery resources aimed at elucidating the genetics of common disorders to clinical facilities focused on the genomics of rare diseases and cancer. Research in these areas has delivered a range of highly-publicised diagnostic and therapeutic innovations, but so far the benefits to patients have generally been modest or confined to relatively small populations, and come at a high cost, both financial and human. Meanwhile, a rather different set of promises, focused on economic growth through biomedical innovation, has been instrumental in shaping how the field of genomic medicine has developed, especially within the National Health Service. One consequence has been a blurring of the distinction between medical care and biomedical research, with genomic medicine patients and their data increasingly being reframed as an economic resource for purposes of commercially-driven innovation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this context, efforts to persuade patients of the personal or public value of research participation, and especially proposals to abandon the principle of clinical non-directiveness in genomic healthcare, raise uncomfortable questions about just whose interests genomic medicine, as currently constituted, is best designed to serve.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"342-353"},"PeriodicalIF":1.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Power and Limitations of Inferring Genetic Ancestry","authors":"Nancy Bird,&nbsp;Turi King,&nbsp;Garrett Hellenthal","doi":"10.1111/ahg.70007","DOIUrl":"10.1111/ahg.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The recent emergence of technologies that capture and analyse genetic variation patterns obtained from a person's DNA sample has led to numerous academic and commercial endeavours to infer individuals' ancestries. In theory, a person's genome contains a wealth of readily accessible information regarding their ancestors, despite only some of our ancestors contributing to the DNA we carry. This makes genetic tests an attractive alternative to the painstaking reconstruction of family trees or directly contacting long-lost relations, particularly when, unless there are notable individuals in the tree, historical and genealogical records tend to diminish in frequency with each generation. However, while powerful, there are limits to what genetic data can unearth, as well as important assumptions underlying these analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review describes some of the early history and latest advances in techniques and data used to infer ancestry using genetics, highlighting both the power and limitations of current studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While genetics is a powerful means of exploring aspects of people's ancestry, a stronger focus on conveying uncertainty will allow both academics and non-academics to avoid the ever-present risks of over-interpretation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"264-273"},"PeriodicalIF":1.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Expert Judgment to Structured Guidelines: A Brief History and Bright Future of DNA Variant Interpretation","authors":"Andreas Laner,&nbsp;Bin Alwi Zilfalil,&nbsp;Sherifa Ahmed Hamed,&nbsp;Huy Do,&nbsp;Iscia Lopes-Cendes,&nbsp;Tilak Shrestha,&nbsp;Edward Tobias,&nbsp;Angela Solano,&nbsp;Ada Hamosh,&nbsp;Dhavendra Kumar","doi":"10.1111/ahg.70009","DOIUrl":"10.1111/ahg.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The classification of sequence variants is at the core of human genetic diagnostics and is the basis for clinical guidance - incorrectly classified variants may cause great harm to patients and their families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We provide an overview of the evolution of ideas and algorithms that have led to the formulation of elaborate classification systems over the last decades, culminating in the ACMG/AMP classification system. Furthermore, we address a still unsolved problem in the clinical translation of DNA analyses: variants of unclear significance (VUS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Rigorous data sharing and the sub-categorisation of VUS could facilitate a clearer interpretation of VUS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review underscores the efforts of the HUGO Education Committee to empower professional—sespecially in resource-limited settings—with the expertise needed for high-quality variant interpretation, fostering equitable access to the transformative potential of genomic medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"372-383"},"PeriodicalIF":1.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}