Search Results (7,535)

Background/Objectives: Non-indigenous species are increasingly reshaping Mediterranean marine ecosystems, particularly under ongoing climate warming. The rayed pearl oyster Pinctada radiata, a thermophilic species originating from the Indo-Pacific region, is one of the earliest and most successful invaders in the Mediterranean Sea and has recently established populations in the Adriatic Sea. Methods: This study integrates preliminary shell morphometric data with molecular genetic analyses based on mitochondrial cytochrome c oxidase subunit I (COI) and nuclear internal transcribed spacer 2 (ITS2) markers to confirm species identity and examine patterns of genetic variation in comparison with other Mediterranean Sea regions and the Persian Gulf. Results: Phylogenetic analyses based on COI confirmed P. radiata as a distinct and well-supported monophyletic lineage, whereas the nuclear ITS2 marker showed limited resolution and interspecific overlap. Mediterranean and Adriatic populations showed low COI haplotype and nucleotide diversity and weak genetic structuring, consistent with recent colonization and secondary expansion, whereas Persian Gulf populations were more genetically diverse. Conclusions: Future studies should employ larger sample sizes and broader geographic sampling across both the Mediterranean Sea and the full native range of P. radiata, combined with high-resolution genome-wide nuclear markers, to better resolve connectivity and invasion dynamics. Full article

Background: Breast cancer (BC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide, thereby posing a substantial threat to women’s health worldwide. However, clinically robust diagnostic biomarkers with high sensitivity and specificity, as well as well-validated molecular targets for targeted therapy, remain limited. Methods: BC transcriptomic data from seven GEO datasets and the TCGA-BRCA cohort (n = 1231) were integrated for analysis. After batch-effect correction, candidate genes were screened through DEA, WGCNA, and PPI networks analysis. An ensemble machine learning (ML) framework incorporating 127 algorithmic combinations was constructed, and SHAP analysis was applied to identify hub genes. Further analyses included functional enrichment, immune infiltration, miRNA regulatory network analysis, and SMR analysis. The expression patterns were validated using single-cell transcriptome data. Drug repositioning analysis and AI-assisted virtual screening were performed to prioritize compounds with favorable drug-like properties. The predicted binding modes of candidate compounds with CHEK1 were assessed by molecular docking. Results: Thirty core genes were obtained through differential expression, WGCNA, and PPI screening. Integrated ML (127 algorithms) determined the optimal model (AUC = 0.919), and SHAP identified nine feature genes, among which CHEK1 and KIF23 showed preliminary diagnostic potential across four external cohorts (AUC: 0.625–0.938). Functional enrichment indicated that both are enriched in the cell cycle and p53 pathways, closely associated with BRCA1/ATR; immune infiltration revealed significant correlations with macrophages and CD8⁺ T cells, with hsa-miR-15a-5p and hsa-miR-607 being common upstream regulatory miRNAs. SMR analysis supported a causal relationship between CHEK1 expression and BC genetic susceptibility (p_SMR < 0.05, p_HEIDI > 0.05); single-cell analysis confirms its heterogeneous expression. AI-assisted virtual screening identified 25 A-grade computational candidate compounds from 171 candidates. Molecular docking suggested that Olaparib and LY294002 can form favorable interactions with the CHEK1 active pocket. Conclusions: The study identified CHEK1 as a key diagnostic gene for BC through 127 ML algorithms and SMR causal inference. By combining AI-assisted virtual screening and molecular docking, computational candidate compounds targeting CHEK1 were prioritized. These findings represent hypothesis-generating in silico predictions and require experimental validation before any therapeutic conclusions can be drawn. Full article

Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics—including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies—have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70–80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology. Full article

Background/Objectives: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency represents the mildest form of congenital adrenal hyperplasia and is frequently diagnosed only after the onset of clinical signs in childhood. Newborn screening programs for CAH are primarily designed to detect classical forms and show limited sensitivity for NCCAH. The clinical significance of neonatal 17-hydroxyprogesterone (17-OHP) values below recall thresholds remains incompletely defined. Methods: We retrospectively analyzed clinical, auxological, hormonal, and genetic data from pediatric patients diagnosed with NCCAH between 2018 and 2023 at a tertiary referral center. Neonatal screening 17-OHP concentrations, basal and ACTH-stimulated 17-OHP levels at diagnosis, bone age advancement, pubertal status, and hydrocortisone treatment were evaluated. Correlations between hormonal parameters, age at onset, and treatment dose were assessed. Results: Thirty-five patients (30 females) were included, with a mean age at clinical onset of 7.52 ± 0.36 years for females and 6.25 ± 0.29 years for males. Premature pubarche was the most frequent presenting sign (94.3%), and central precocious puberty was diagnosed in 31.4% of cases. The mean neonatal screening 17-OHP level was 4.53 ± 0.7 ng/mL; only two patients exceeded the screening recall cut-off. At diagnosis, mean basal and ACTH-stimulated 17-OHP levels were 15.1 ± 3.35 and 55.2 ± 11.3 ng/mL, respectively. Age at clinical onset was inversely correlated with both basal and stimulated 17-OHP levels, while hydrocortisone dose correlated positively with biochemical severity. Bone age advancement was observed in all patients. Conclusions: Most children with NCCAH display mildly elevated neonatal 17-OHP values that do not trigger screening recall. Higher biochemical severity is associated with earlier clinical presentation and higher glucocorticoid requirements. Neonatal 17-OHP concentrations, even when below cut-off values, may represent an early indicator of disease severity and warrant further investigation. Full article

Fusarium ear rot (FER) caused by Fusarium verticillioides is a major constraint on global maize production. The genetic basis of FER resistance is not yet fully understood, and the development of effective breeding strategies for improving FER resistance is still a critical priority. In the present study, a collection of 254 CIMMYT tropical maize lines genotyped with 955,690 high-quality SNPs was used to conduct genome-wide association studies (GWAS), complemented by QTL (quantitative trait locus) mapping in two recombinant inbred line populations. Additionally, genomic prediction (GP) exploring various statistical models and SNP selection schemes was implemented to optimize predictive accuracy for improving FER resistance. The broad-sense heritability estimates of FER resistance were 0.69–0.86 in the CML panel across six environments and 0.39–0.69 in the two RIL populations. At a p-value threshold of 2.61 × 10⁻⁷, GWAS identified 18 SNPs significantly associated with FER resistance across six environments, and in single environment analyses, their phenotypic variance explained (PVE) values ranged from 0.68 to 13.75%, with 13 SNPs exceeding a PVE of 5%. At a p-value threshold of 1 × 10⁻⁵, an additional 37 SNPs were detected, clustering within seven environmentally stable regions identified in at least two environments. Furthermore, 13 haplotype blocks exhibiting significant phenotypic differences were identified within these stable regions, with PVE values ranging from 2.39 to 15.24%, 9 of which exceeded 5%. QTL mapping in the two RIL populations revealed 27 moderate-effect QTLs at a LOD threshold of 2.5, including four detected repeatedly across environments, though only one QTL overlapped with the GWAS-identified region. Moderate genomic prediction accuracies of FER severity were achieved across models, with GBLUP and BayesB outperforming other models, and the prediction accuracies of these two models in the three populations were all around 0.5. Integrating the significant SNP set from genetic mapping results with a 100-SNP background set enhanced the stability of cross-population predictions. These results implied that FER resistance in tropical maize is controlled by multiple genomic regions with small-to-moderate genetic effects, whereas the consistency of genomic regions detected by GWAS and QTL mapping is low. Genomic prediction incorporating regions identified across different genetic backgrounds emerges as a promising tool for accelerating FER resistance breeding. Full article

Background: Early childhood caries (ECC) is one of the most common chronic diseases in children and remains unevenly distributed across populations. It is associated with pain, impaired function, and long-term health consequences. Although advances have been made in understanding its aetiology and prevention, important gaps in evidence limit progress in prevention, early detection, and equitable care. Objective: To examine current evidence on ECC and identify key research gaps across biological, behavioral, social, and health system domains. Methods: This narrative review draws on peer-reviewed literature addressing ECC epidemiology, pathogenesis, risk factors, diagnosis, management, and service delivery. The literature was examined to identify areas where evidence is limited, inconsistent, or insufficient to inform clinical practice and public health policy. Results: Research on ECC remains uneven across levels. Longitudinal evidence linking microbiome dynamics, host susceptibility, and lesion progression is limited, restricting causal understanding. Genetic and epigenetic contributions are incompletely defined, particularly in diverse populations. Although socioeconomic gradients are well established, integrative models connecting structural determinants with biological mechanisms are scarce. Emerging diagnostic tools, including biomarkers and artificial intelligence, lack robust evidence demonstrating improved clinical or behavioral outcomes. Implementation research addressing scalability, cost-effectiveness, and equity impact is underdeveloped, especially in low-resource settings. Long-term systemic and developmental consequences of ECC remain insufficiently characterized. Conclusions: Addressing ECC requires integrated and equity-oriented research frameworks that bridge biological, social, diagnostic, and implementation domains. Clarifying these gaps is essential to inform coherent prevention strategies and reduce persistent disparities in child oral health. Full article

Background/Objectives: Acute promyelocytic leukemia (APL) is a high-risk subtype of acute myeloid leukemia and requires rapid diagnosis to avoid early mortality. Current clinical diagnostic and genetic tests are time-consuming, expensive, and complex. Notably, all these tests depend on bone marrow aspiration and are intensely invasive, resulting in poor patient compliance. This study aimed to develop a rapid, explainable, and accurate auxiliary tool for cell-level detection of abnormal promyelocytes in peripheral blood smears, which can serve as a key clue for suspecting APL. Methods: We developed a multi-stage deep learning (DL) model that automatically read images of peripheral blood smears (PBSs), accurately segmented cells, and identified abnormal promyelocytes using only image data. We retrospectively reviewed a total of 114 bone marrow smears (42 APL patients and 72 non-APL patients) and 158 PBSs (30 APL patients and 128 non-APL patients) at the Fifth Affiliated Hospital of Harbin Medical University and collected 223,123 cell images for training. Then, the efficacy of EfficientDet in APL screening was evaluated with an additional 150 PBSs (50 from APL patients and 100 from non-APL patients) and finally compared with manual microscopy. Results: EfficientDet exhibited superior overall screening performance compared with pathologists in the identification of abnormal promyelocytes. Conclusions: Our findings suggest that the DL approach we describe herein is promising as a practical tool for abnormal promyelocyte detection and early APL screening, raising attention to suspected cases of APL for expert evaluation and further reducing diagnostic delays. Full article

Background: Bone and soft tissue sarcomas, while rare, making up less than 2% of adult cancers with an incidence below 5 per 100,000 annually, present a significant challenge due to their varied and often obscure pathology. Additionally, the absence of global sarcoma awareness contributes to delayed interventions, necessitating more-aggressive treatments and increasing mortality risks. Conversely, cancers such as breast and colon have seen improved outcomes through effective screening and early-management strategies. Methods: In this cross-sectional study, out of the total number of participants approached, using a preset questionnaire, by trained medical students to participate in this study, 626 met the inclusion criteria. The questionnaire started with an informed consent process followed by a set of questions regarding sociodemographic characteristics and lifestyle. Subsequently, the questionnaire delved into their understanding and awareness of bone and soft tissue sarcomas, focusing on risk factors, recognizable signs and symptoms, and tendencies regarding health-seeking behavior. Results: In this study with 626 participants, demographic insights showed a young cohort, with 43.5% between 21 and 30 years, and a male predominance of 60.1%. Risk factor awareness was moderate; genetics and smoking were recognized as primary risks for sarcomas. Participants showed limited awareness of sarcoma signs, symptoms, and management, with a substantial percentage unsure about the most at-risk age group, gender differences in risk, and recognizability of symptoms. Barriers to seeking medical care included a passive attitude towards healthcare, fear, and accessibility issues. Most participants had limited knowledge of sarcomas, with 58% unaware of risk factors and 72.3% of signs and symptoms. Conclusions: This study emphasizes the necessity for targeted interventions to bridge the knowledge gap and promote early detection practices, which could significantly impact the prognosis of sarcoma patients. Full article

Background: Improved assessment of tumor biology has contributed to better outcomes in colorectal liver metastasis (CLM). Previously, tumor biology was assessed based on clinical factors such as number and size of metastases, primary tumor characteristics, and extent of extrahepatic disease. Currently, tumor biology assessment includes response to chemotherapy, genetic mutations, and circulating tumor DNA (ctDNA). Methods: A review of the literature in Medline/Pubmed, Embase, and Cochrane Library was conducted using keywords and MeSH terms. Results: Tumor response to chemotherapy can be assessed using pathologic and radiologic criteria. Radiologic morphologic response has been associated with more accurate determination of outcomes compared with size-based criteria. Pathologic tumor response can be assessed by the percentage of cancer cells remaining within each tumor, the ratio of cancer cells to fibrosis, and the thickness of the tumor–normal liver interface. Six driver mutations are consistently associated with outcomes in CLM: RAS/BRAF, TP53, SMAD4, FBXW7, and APC. All are associated with decreased overall survival (OS) and recurrence-free survival (RFS) except for APC, which is associated with better survival. More than 50% of patients have co-mutations, and a three-tier pathway-centric risk score integrating these mutations offers a more comprehensive approach. While mutations should be considered when evaluating for locoregional therapy, it should not influence ablation margins, surgical margins, or parenchymal sparing approach. Preoperative ctDNA is associated with worse survival, but clearance after hepatectomy is associated with improved survival. Postoperative ctDNA status is associated with recurrence and has the potential to guide the choice of adjuvant chemotherapy. Conclusion: Tumor biology enables informed, precise, and personalized decision-making. Integration of response to chemotherapy, driver mutations, and ctDNA into routine practice is critical to improve CLM management. Full article

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), glial cell line-derived neurotrophic factor (GDNF), and proinsulin—have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable. Full article

Background/Objectives: Early-onset high myopia (eoHM), defined as high myopia manifesting before 10 years of age, is largely attributed to genetic defects. This study aimed to investigate the genetic underpinnings of eoHM in a cohort of Chinese patients. Methods: We recruited 64 Chinese patients with eoHM. Comprehensive clinical evaluations were performed, and whole exome sequencing (WES) was conducted to identify potential pathogenic variants. The genetic findings were analyzed and correlated with the clinical phenotypes. Results: A total of 64 unrelated Chinese patients with suspected early-onset high myopia were initially recruited. Following whole exome sequencing (WES) and variant annotation, final 37 patients with variants in known myopia-associated genes were included in the analytical cohort. The mean age of onset for the cohort was 5 years (IQR, 4–7), with a mean spherical equivalent refraction of −7 D (IQR, (−8)–(−6)). Genetic analysis revealed variants in 28 known myopia-associated genes. We identified pathogenic or likely pathogenic variants in 11 of the 37 patients (29.7%, 95%CI: 0.1737–0.4590), while the overall diagnostic yield was 17.2% (11/64, 95%CI: 0.0970–0.2839) in initial 64 recruited patients. These genes included seven well-established eoHM-related genes, such as ARR3, CACNA1F, P4HA2, TRPM1, COL11A1, COL2A1, and PAX6. Additionally, variants of uncertain significance (VUS) in seven other candidate genes were detected in patients with eoHM. Conclusions: Our findings expand the genetic spectrum of eoHM and reinforce the critical role of genetic testing in its etiological diagnosis and clinical management. Observed patterns of genotype–phenotype associations are descriptive and should be considered hypothesis-generating, requiring validation in larger cohorts. Additionally, we identify several candidate genes that may serve as prospective biomarkers, though these findings require validation in larger cohorts and functional studies. Full article

Background/Objectives: Contralateral breast cancer (CBC) is a significant concern among breast cancer survivors, particularly in those with moderator-high penetrance germline mutations such as BRCA1, BRCA2, CHEK2, and ATM. While radiotherapy (RT) is a crucial component of breast cancer (BC) treatment, its potential role in increasing CBC risk remains unclear. This systematic review and meta-analysis aim to evaluate the incidence of radiation-induced CBC in germline mutation carriers. Methods: Following PRISMA guidelines, we conducted a comprehensive search in six electronic databases (PubMed, Scopus, Cochrane Library, ProQuest, EBSCO, and Epistemonikos) for studies published fifteen years prior, up to August 2025. We included cohort and case–control studies assessing the association between RT and CBC incidence in germline mutation carriers. A meta-analysis was performed using a random-effects model to estimate cumulative risk (CR) and rate ratios (RR). Results: Seven studies were included. The 5-year cumulative risk (CR) of contralateral breast cancer (CBC) was 0.55 for BRCA1/2, 0.89 for ATM, and 0.80 for CHEK2 carriers. At 10 years, overall CR increased to 0.65, with ATM and CHEK2 remaining high. Rate ratio (RR) analysis showed a significant risk for ATM (2.98), while overall RR indicated more than a two-fold increased CBC risk with radiotherapy (RR = 2.70 common-effect; 2.53 random-effects). Conclusions: Radiotherapy significantly increases contralateral breast cancer risk, particularly in ATM and CHEK2 carriers, emphasizing the importance of personalized genetic risk stratification in treatment decisions. Full article

Tuberculosis (TB) remains a major public health challenge in Peru, where interindividual variability in treatment response and drug-induced hepatotoxicity may be influenced by host genetic background. This study aimed to characterize clinically relevant polymorphisms in NAT2, CYP2E1, and SLCO1B1 in a cohort of TB patients from Southern Peru, a genetically underrepresented Andean population. Thirty-five adults receiving first-line therapy (isoniazid and rifampicin) underwent targeted Sanger sequencing of key functional variants among these three genes. NAT2 acetylator phenotypes were predominantly intermediate (68.6%), followed by rapid (20%) and slow (11.4%) profiles, with high minor allele frequencies for rs1041983 and rs1801280. CYP2E1 functional promoter variants were infrequent, whereas SLCO1B1 exhibited notable allelic heterogeneity, suggesting potential variability in rifampicin transport. Comparative analysis with previously reported Peruvian data revealed regional differences in acetylator distribution, supporting population-specific pharmacogenomic stratification. Although clinical toxicity outcomes were not evaluated, the high prevalence of reduced acetylation genotypes suggests a substantial proportion of patients may benefit from genotype-informed isoniazid dosing strategies. These findings provide foundational data for implementing precision medicine approaches using affordable and targeted technologies in TB management within Andean populations and support the integration of pharmacogenomics into national TB control programs. Full article

Background: Genetic diversity and genetic differentiation between Gossypium hirsutum-Gossypium barbadense introgression lines (ILs) and early-maturing upland cotton lines are critical for resolving the core breeding contradiction in Xinjiang cotton region: narrow genetic basis of early-maturing cultivars and late maturity of ILs with superior fiber quality. Xinjiang is one of the major cotton-producing regions in China, and breeding high-quality early-maturing upland cotton adapted to local ecological conditions is essential for improving cotton yield and quality. However, the genetic relationship and differentiation between the two types of cotton germplasm remain unclear, which hinders the efficient utilization of germplasm resources in breeding. Therefore, this study aimed to clarify the genetic diversity and differentiation between the two germplasm types and identify key candidate loci related to early maturity and fiber quality, providing support for cotton breeding. Results: Here, we used a 40K Single Nucleotide Polymorphism chip to genotype core cotton germplasm in northern Xinjiang, and analyzed their population structure, genetic diversity and functional SNP loci associated with early maturity and fiber quality. The tested materials were clearly divided into two subgroups (ILs and early-maturing lines). Genetic diversity analysis revealed a significantly narrow genetic basis in the early-maturing subgroup, while the IL subgroup had higher genetic diversity. Specifically, the early-maturing subgroup showed lower nucleotide diversity and polymorphism information content compared with the IL subgroup, indicating that the genetic variation of early-maturing cotton germplasm in northern Xinjiang is relatively limited. A total of 25 non-synonymous SNPs were identified, among which the c.A613G:p.T205A mutation in GH_D09G1484 (mRNA-decapping enzyme 1, DCP1) was a characteristic variation of early-maturing cotton, and a possible non-synonymous mutation in GH_A09G2400 (Heat shock transcription factor A6b, HSFA6B) was associated with fiber development. These two candidate genes were annotated to be involved in plant growth and development, further supporting their potential roles in regulating cotton early maturity and fiber quality. Conclusions: This study clarified the genetic differentiation between the two types of germplasms and identified key candidate loci for early maturity and fiber quality, providing precise molecular markers and theoretical support for breeding high-quality early-maturing upland cotton adapted to Xinjiang’s ecological conditions. The results also highlight the value of Gossypium hirsutum–Gossypium barbadense introgression lines in enriching the genetic basis of early-maturing cotton, which can be further utilized to solve the core breeding contradiction in the Xinjiang cotton region. Full article

Background: Sarcopenia is the age-related, progressive loss of strength, function, and skeletal muscle mass, which can be assessed with specific tests. The Growth differentiation factor 15 (GDF-15) has been proposed as a key biomarker of aging, and it has been associated with mitochondrial dysfunction, cachexia, and physical impairment. Methods: The cohort of this study comes from the SardiNIA study, an ongoing longitudinal survey focused on the identification of genetic and phenotypic variants associated with aging. We assessed hand grip strength, gait speed, and GDF-15 in all samples. Linear multivariate analysis was used to assess the correlation after adjusting for a range of potential confounders. Results: The sample consisted of 4842 subjects (57.5% female) with a median age of 48.6 years. Levels of GDF-15 were comparable between males and females and showed a strong positive association with aging (rho 0.617, p < 0.001). Linear multivariate regression analyses showed that GDF-15 was negatively associated with gait speed and grip strength in both hands (respectively, Beta −0.09, Beta −0.07, and Beta −0.08, p < 0.001 for all). Conclusions: GDF-15 was negatively associated with physical function. GDF-15 may be considered a proxy for reduced physical performance. Future research is needed to understand the pathogenetic role of GDF-15 in the reduction in skeletal muscle in aging people. Full article