Human Genomics最新文献

{"title":"Toward streamline variant classification: discrepancies in variant nomenclature and syntax for ClinVar pathogenic variants across annotation tools.","authors":"Yu-An Chen, Tzu-Hang Yuan, Jia-Hsin Huang, Yu-Bin Wang, Tzu-Mao Hung, Chien-Yu Chen, Pei-Lung Chen, Jacob Shujui Hsu","doi":"10.1186/s40246-025-00778-x","DOIUrl":"10.1186/s40246-025-00778-x","url":null,"abstract":"<p><strong>Background: </strong>High-throughput sequencing has revolutionized genetic disorder diagnosis, but variant pathogenicity interpretation is still challenging. Even though the human genome variation society (HGVS) provides recommendations for variant nomenclature, discrepancies in annotation remain a significant hurdle.</p><p><strong>Results: </strong>In this study, we evaluated the annotation concordance between three tools-ANNOVAR, SnpEff, and variant effect predictor (VEP)-using 164,549 two-star variants from ClinVar. The analysis used HGVS nomenclature string-match comparisons to assess annotation consistency from each tool, corresponding coding impacts, and associated ACMG criteria inferred from the annotations. The analysis revealed variable concordance rates, with 58.52% agreement for HGVSc, 84.04% for HGVSp, and 85.58% for the coding impact. SnpEff showed the highest match for HGVSc (0.988), while VEP bettered for HGVSp (0.977). The substantial discrepancies were noted in the loss-of-function (LoF) category. Incorrect PVS1 interpretations affected the final pathogenicity and downgraded PLP variants (ANNOVAR 55.9%, SnpEff 66.5%, VEP 67.3%), risking false negatives of clinically relevant variants in reports.</p><p><strong>Conclusions: </strong>These findings highlight the critical challenges in accurately interpreting variant pathogenicity due to discrepancies in annotations. To enhance the reliability of genetic variant interpretation in clinical practice, standardizing transcript sets and systematically cross-validating results across multiple annotation tools is essential.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"70"},"PeriodicalIF":3.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update of the sideroflexin (SLC56) gene family.","authors":"Angeliki I Katsafadou, Daniel W Nebert, Sergey A Krupenko, David C Thompson, Vasilis Vasiliou","doi":"10.1186/s40246-025-00779-w","DOIUrl":"10.1186/s40246-025-00779-w","url":null,"abstract":"<p><p>The human sideroflexin (SFXN) gene family, also classified as solute carrier family 56 (SLC56), encodes a group of five mitochondrial transmembrane proteins (SFXN1-SFXN5) involved in key aspects of mitochondrial metabolism, cellular homeostasis, and development. SFXNs are highly conserved across eukaryotic species, with evolutionary the origin traced back to the earliest metazoans. Functionally, each of the five family members exhibits distinct functional specialization. Particularly, SFXN1 and SFXN3 facilitate mitochondrial serine transport, supporting one-carbon metabolism. SFXN2 and SFXN4 are implicated in mitochondrial iron regulation, heme biosynthesis, and iron-sulfur cluster assembly. SFXN5, predominantly expressed in the brain, is proposed to regulate citrate metabolism and immune cell functions. Mutations or dysregulation of SFXN genes have been linked to certain human diseases, including congenital sideroblastic anemia, oxidative phosphorylation disorders, neurodegenerative conditions, and cancers. Structurally, SFXNs share conserved transmembrane domains and key motifs critical for substrate transport, mitochondrial iron homeostasis, and overall mitochondrial function. The evolutionary trajectory of the SFXN family-from amino acid transport to functionally specialized roles in higher organisms-highlights their biological and clinical significance. Comparative studies across model organisms reveal both conserved and divergent functions, emphasizing their importance in health and disease. A comprehensive understanding of the SFXN family not only advances fundamental mitochondrial research but also opens avenues for novel therapeutic interventions.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"69"},"PeriodicalIF":3.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHEK1 variant is a risk factor for premature ovarian insufficiency by mis- regulating metabolism and inflammation-related genes.","authors":"Jianying Guo, Yali Fan, Zifan Song, Lin Li, Meng Fu","doi":"10.1186/s40246-025-00774-1","DOIUrl":"10.1186/s40246-025-00774-1","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is affecting approximately 1% of females and increasingly contributing to female infertility. The etiology of POI is heterogeneous. CHEK1, a critical component of the DNA damage and replication stress response, has recently been linked to female reproductive biology.</p><p><strong>Results: </strong>We identified a CHEK1 variant c.77C > G; p.A26G in a POI patient through whole-exome sequencing. Protein structure prediction and pathogenicity analysis suggested that the CHEK1 A26G variant may affect protein stability. RNA sequencing results of 293FT cells overexpressing wild-type and A26G CHEK1 revealed altered expression and alternative splicing of genes involved in metabolism and inflammation.</p><p><strong>Conclusion: </strong>CHEK1 may be involved in ovarian aging and the A26G variant may increase susceptibility to POI.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"67"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of genetic testing for Usher syndrome in a diverse population cohort from South Florida.","authors":"Zachary J Cromar, Ryan Chen, Tamara Juvier Riesgo, Denise Yan, Lindsay Dawn Verma, Zhengyi Chen, Susan H Blanton, Byron L Lam, Xue Zhong Liu","doi":"10.1186/s40246-025-00775-0","DOIUrl":"10.1186/s40246-025-00775-0","url":null,"abstract":"<p><strong>Background: </strong>Usher syndrome (USH) is the leading genetic cause of congenital deaf blindness worldwide. USH is an autosomal recessive disorder clinically characterized by partial or complete congenital sensorineural hearing loss followed by progressive vision loss due to retinitis pigmentosa. There are three main subtypes (USH1, USH2, USH3) with different genetic causes categorized by age of symptom onset and severity. Understanding the genetic epidemiology of USH can help identify novel mutations and facilitate definitive diagnosis and treatment. This retrospective study characterizes the mutation spectrum of USH in an ethnically diverse South Florida population.</p><p><strong>Results: </strong>Of the 148 patients assessed for this study, 67 were male and 81 were female. In this population, one identified as American Indian or Alaska Native, 6 identified as Asian (A), eight identified as Black or African American (AA), eight identified as More than One Race, 26 were identified as Unknown or Not Reported, and 99 were identified as white. In addition, 42 identified as Hispanic or Latino, 87 identified as Non-Hispanic or Latino, and 19 were identified as Unknown or Not Reported; all individuals identifying as Hispanic or Latino were either White or Unknown. One American Indian or Alaska Native patient, two Asian patients, two Black or African American Patients, and 15 white patients had inconclusive molecular testing results. In our population, White Non-Hispanics were more likely to receive a conclusive molecular diagnosis for their hearing loss.</p><p><strong>Conclusions: </strong>This is the first genetic characterization of an ethnically diverse South Florida population with USH, which can help direct patient diagnosis and medical care. As clinical trials for treatment increases, molecular testing in all individuals is imperative.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"68"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients.","authors":"Rania A Zahwo, Ziad N Rezk, Tamer M Elwasify, Amr M Zaki, Hoda M El Assi, Eman Ramadan, Abdallah Y Habib, Wael A Hassan, Ahmed Abdel-Raouf, Ameera Ragheb, Amin F Shaker, Khaled E Amer, Heba Sh Kassem","doi":"10.1186/s40246-025-00769-y","DOIUrl":"10.1186/s40246-025-00769-y","url":null,"abstract":"<p><strong>Background: </strong>Familial Hypercholesterolemia (FH) is a major risk factor for premature Coronary Artery Disease (CAD). Genetic testing is the gold standard for FH diagnosis. The purpose of this Observational Analytical Cross-sectional study was to estimate the proportion of genetically confirmed Familial Hypercholesterolemia in Patients with premature Coronary Artery Disease in a cohort of Egyptian patients.</p><p><strong>Methods: </strong>Next generation sequencing (NGS) was conducted for 7 genes (LDLR, PCSK9, APOB, APOE, ABCG5, ABCG8 and LDLRAP1) commonly associated with FH in 94 patients with Premature CAD from 2 tertiary hospitals in Cairo and Alexandria, Egypt. Individuals were clinically assessed using the Dutch Lipid Network criteria and genetically-confirmed FH prevalence was analyzed.</p><p><strong>Results: </strong>Fourteen patients had pathogenic or likely pathogenic mutations in LDLR, APOB, PCSK9 and LDLRAP1 genes. Three patients had homozygous autosomal dominant FH and another 3 patients had autosomal recessive hypercholesterolemia. In addition, 10 patients had rare variants of uncertain significance in LDLR, APOB, APOE, ABCG5 and ABCG8 genes.</p><p><strong>Conclusions: </strong>The prevalence of genetically confirmed FH in premature CAD (PCAD) patients in this study was found to be 14.89%. The Dutch Lipid Clinic Network (DLCN) scoring system is suggested as a good screening tool for familial hypercholesterolemia but confirmatory genetic testing is essential for the accurate diagnosis and management of the patients. In Egypt, the high rate of consanguinity contributes to the high prevalence of both homozygous autosomal dominant and recessive FH.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"66"},"PeriodicalIF":3.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved breast cancer risk prediction using chromosomal-scale length variation.","authors":"Yasaman Fatapour, James P Brody","doi":"10.1186/s40246-025-00776-z","DOIUrl":"10.1186/s40246-025-00776-z","url":null,"abstract":"<p><strong>Introduction: </strong>Early diagnosis of breast cancer leads to higher long-term survival rates. The development of a germline genetic test, or polygenic risk score, to identify women at high risk of breast cancer holds the potential to reduce cancer deaths. However, current tests based on SNPs do not perform much better than predictions based on family history and perform significantly worse in populations with non-European ancestry. We have developed an alternative method to characterize a genome, called chromosomal-scale length variation, which can be applied to polygenic risk scores.</p><p><strong>Objective: </strong>The objective of this paper is to characterize a breast cancer genetic risk score based on chromosomal-scale length variation using the NIH All of Us dataset in different self-identified racial groups when trained on different populations.</p><p><strong>Methods: </strong>We used the NIH All of Us dataset to compile a dataset with 4,533 women who have been diagnosed with breast cancer (including 440 who self-identified as Black) and 44,518 women who have not. We acquired, through All of Us, genetic information for each of these women. We computed a set of 88 values for each woman in the dataset, representing the chromosomal-scale length variation parameters. These numbers are average log R ratios for four different segments from each of the 22 autosomes. We used machine learning algorithms to find a model that best differentiates the women with breast cancer from the women without breast cancer based on the set of 88 numbers that characterize each woman's germline genome.</p><p><strong>Results: </strong>The best model had an AUC of 0.70 (95% CI, 0.67-0.73) in the All of Us population. Women who scored in the top quintile by this model were nine times more likely to have breast cancer when compared to women who scored in the lowest quintile.</p><p><strong>Conclusion: </strong>In conclusion, we found that this method of computing genetic risk scores for breast cancer is a substantial improvement over SNP-based polygenic risk scores. In addition, we compared models trained on populations of only White women and only Black women. We found that the models trained only on White women performed better than models trained only on Black women when tested on only White women. We did not see a significant difference between the two models when tested on only Black women.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"65"},"PeriodicalIF":3.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parents' perspectives on expanded newborn genomic screening in Abu Dhabi, United Arab Emirates.","authors":"Yasir Ahmed Mohammed Elhadi, Marwa Alkatheeri, Maryam Alktifan, Fatma Alhammadi, Taif Sultan, Yousef M Abu Alqumboz, Ahmed Jihad, M Islam Shaidul, Mohammed Al Saadi, Meera Saeed Nhayah Alkaabi, Khalid Almaamari, Khalifa Alseiari, Naser Alshamsi, Omar Alzaabi, Saoud Al Tamimi, Mohamed Salem Alameri, Emad Masuadi, Azhar T Rahma","doi":"10.1186/s40246-025-00766-1","DOIUrl":"10.1186/s40246-025-00766-1","url":null,"abstract":"<p><strong>Background: </strong>Newborn genomic screening offers the potential for early detection and management of genetic disorders. Understanding parental perspectives is essential before integrating genomic testing into standard newborn screening.</p><p><strong>Methods: </strong>This was a descriptive cross-sectional study surveyed 568 parents in Abu Dhabi, United Arab Emirates (UAE). An online self-administered validated and piloted questionnaire was used to gather information on demographic characteristic and perspectives regarding newborn genomic screening. Data were analysed using R version 4.4.3.</p><p><strong>Results: </strong>Most parents (78.2%) supported integrating genomics into newborn screening programs, with 63.5% stating it requires distinct management from standard screening. Females preferred geneticists (38.2% vs. 32.5%, p < 0.001) and hospitals (45.1% vs. 39.2%, p < 0.001) for discussions, with 74.2% emphasizing explicit consent compared to 68.5% of males (p < 0.002). Treatability (82.7%), age of symptom onset (74.1%), and severity (72.2%) were key decision-making factors. Additionally, 66.7% preferred genomic testing to be covered by insurance, and 82.2% supported storing genomic data for future use.</p><p><strong>Conclusion: </strong>Parents participated in the study strongly support genomic newborn screening. Gender-based differences emphasize the need for tailored communication and culturally sensitive strategies to inform policy development and implementation of newborn genomic screening program in the UAE and similar contexts.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"63"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Genomics Brief Reports: embracing concise dissemination for rapid and impactful discoveries.","authors":"Vasilis Vasiliou, Juergen K V Reichardt, Bassam R Ali","doi":"10.1186/s40246-025-00777-y","DOIUrl":"https://doi.org/10.1186/s40246-025-00777-y","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"64"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes.","authors":"Inger Johansson, Yuchen Lu, Yitian Zhou, Kristi Krebs, Martina Akcan, Lili Milani, Magnus Ingelman-Sundberg","doi":"10.1186/s40246-025-00765-2","DOIUrl":"10.1186/s40246-025-00765-2","url":null,"abstract":"<p><strong>Background: </strong>Variations in pharmacogenes that regulate drug absorption, distribution, metabolism, and excretion (ADME) contribute to approximately 20-30% of interindividual differences in drug response. While many common variants are successfully utilized in clinical settings to predict individual drug responses, a significant portion of the genetic basis underlying this variability remains unidentified. This includes rare variants, which are estimated to account for 4-6% of drug response variability.</p><p><strong>Results: </strong>To comprehensively elucidate the functional consequences and molecular mechanisms of rare variants, we conducted in vitro enzyme expression studies combined with in silico structure-function analyses. We selected 11 rare variants in the CYP2C19 and CYP2D6 genes identified among participants within the Estonian Biobank. Variant cDNAs were heterologously expressed in HEK-293 cells, and detailed enzyme activity analyses were performed. The experimental results were further validated against average scores from five optimized in silico prediction models: LRT, Mutation Assessor, PROVEAN, VEST3, and CADD. To explore structure-activity relationships, we performed in silico docking of substrates into available 3D enzyme structures. Our findings reveal that most of the rare genetic variants caused significant functional alterations, including: (i) Likely impairments in substrate transport to the active site due to narrowing of access channels; (ii) Changes in catalytic rates; and (iii) Potential effects on substrate extrusion rates from the active site. The in silico prediction tools accurately anticipated the functional impact of 6 out of the 11 variants (54%).</p><p><strong>Conclusions: </strong>Evaluating the functionality of rare variants will become increasingly essential as rapid and cost-effective whole-genome sequencing technologies continue to advance. Our results highlight the need for further refinement of in silico prediction models, particularly those leveraging 3D crystal enzyme structures, to enhance the accuracy of functional predictions for rare genetic variants.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"62"},"PeriodicalIF":3.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers.","authors":"Paul Fabian, Gil Blander, Renee Deehan, Ali Torkamani, Bartek Nogal","doi":"10.1186/s40246-025-00756-3","DOIUrl":"10.1186/s40246-025-00756-3","url":null,"abstract":"<p><strong>Background: </strong>The interplay between diet and healthspan is a topic of great interest in biomedical research. Toward this end, consumption of marine omega-3 fatty acids is of particular significance, as reports suggest that diets focused on seafood can prolong the disease-free portion of the human lifespan. Fish consumption has also been linked to reduced biological aging as measured by epigenetic clocks, but there is no conclusive evidence of a causal relationship. Moreover, fish oils reduce triglycerides, and may affect other lipid profiles, as well as systemic inflammation. To investigate further, we used two-sample Mendelian randomization to investigate potential causality between fish intake and healthspan markers.</p><p><strong>Methods: </strong>Bidirectional Mendelian randomization was performed in the two-sample setting with publicly available GWAS summary statistics. GWAS data from the UK Biobank for oily fish consumption (n = 460,443) and fish oil supplementation (n = 461,384) were used as the primary exposures. First-generation epigenetic clocks Hannum age and intrinsic epigenetic age acceleration (IEAA), as well as second-generation clocks GrimAge and PhenoAge were collected from an independent dataset of individuals of European ancestry (n = [34,449-34,667]). Finally, data from the Integrative Epidemiology Unit database was used for serum proxies of lipidemia and systemic inflammation (n = [61,308-78,700]). Additional sensitivity analyses, such as reverse causation testing and the Cochran's Q test were performed for exposure-outcome pairs where the inverse variance weighted (IVW) method was significant (p-value < 0.05), and where the MR Egger method indicated an effect in the same direction as the IVW result.</p><p><strong>Results: </strong>We report that oily fish consumption appears to decrease PhenoAge acceleration (p < 0.0086), whereas fish oil supplementation appears to decrease GrimAge (p <math><mo>=</mo></math> 0.037). Both omega-3 exposures modify the epigenetic clocks in the expected negative, or age-decelerating, direction. For the serum biomarkers, we find evidence that fish oil consumption leads to a reduction in triglycerides (p <math><mo>=</mo></math> 0.004), although HDL and LDL were not significantly modified. Finally, we also detected a suggestive inverse relationship between oily fish consumption and hsCRP (p <math><mo>=</mo></math> 0.064).</p><p><strong>Conclusions: </strong>Our analysis shows that consuming fish oil, whether through whole food or as a supplement, can have a rejuvenating impact as measured by PhenoAge and GrimAge acceleration. We have also provided evidence further linking fish oil intake and lower triglyceride levels. These results, based on robust MR-based analyses, emphasize the effectiveness of dietary choices in modifying emerging measures of healthspan.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"61"},"PeriodicalIF":3.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}