Phenomics (Cham, Switzerland)最新文献

High-altitude polycythemia (HAPC) is a prevalent chronic condition affecting individuals at high altitudes, including both highland and plains populations. This study, involving 2248 participants, explored genetic susceptibility to HAPC among ethnic groups, with 898 HAPC patients (450 Han, 448 Tibetan). The Genome-wide Association Study, encompassing 198 cases (100 Han, 98 Tibetan), identified eight Tibetan HAPC-susceptibility single-nucleotide polymorphisms and four in Han individuals. The common polymorphism locus rs7618658 (SNX4, p _combine < 5 × 10^-8) was validated in both populations. The investigation of Tibetan EPAS1 revealed the rs1374749 locus, along with linked loci, as a potential prevalence factor for HAPC. The GGTAC haplotype containing this locus emerged as a Protect haplotype for HAPC (p = 2.461 × 10^-12, OR = 0.344). Enrichment analysis revealed that Tibetans exhibited susceptibility in oxygen-sensing pathways, such as EPAS1, associated with phenotypes like hemoglobin and platelets. In contrast, Han Chinese showed significant sensitivity in cell differentiation and angiogenesis, closely linked to hemoglobin, hematocrit, and platelets.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00180-y.

Gut microbiome, the group of commensals residing within the intestinal tract, is closely associated with dietary patterns by interacting with food components. The gut microbiome is modifiable by the diet, and in turn, it utilizes the undigested food components as substrates and generates a group of small molecule-metabolites that addressed as "meta-metabolome" in this review. Profiling and mapping of meta-metabolome could yield insightful information at higher resolution and serve as functional readouts for precision nutrition and formation of personalized dietary strategies. For assessing the meta-metabolome, sample preparation is important, and it should aim for retrieval of gut microbial metabolites as intact as possible. The meta-metabolome can be investigated via untargeted and targeted meta-metabolomics with analytical platforms such as nuclear magnetic resonance spectroscopy and mass spectrometry. Employing flux analysis with meta-metabolomics using available database could further elucidate metabolic pathways that lead to biomarker discovery. In conclusion, integration of gut microbiome and meta-metabolomics is a promising supplementary approach to tailor precision dietary intervention. In this review, relationships among diet, gut microbiome, and meta-metabolome are elucidated, with an emphasis on recent advances in alternative analysis techniques proposed for nutritional research. We hope that this review will provide information for establishing pipelines complementary to traditional approaches for achieving precision dietary intervention.

Ovarian cancer (OC), a predominant gynecological malignancy, has consistently showcased grim prognostic outcomes. This investigation delves into the emerging field of pyroptosis and the intricacies of long non-coding RNAs (lncRNAs), specifically the lesser-studied pyroptosis-related lncRNAs (PRlncRNAs), and their roles in OC prognosis. By harnessing transcriptome, and clinic data from the genotype-tissue expression (GTEx) and the cancer genome Atlas (TCGA), we formulated a unique PRlncRNAs risk model consisting of five prognostic lncRNAs by Cox regression and least absolute shrinkage and selection operator (LASSO) regression. Next, the Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, nomogram, and calibration were implemented to verify and evaluate the model. The model also showed general applicability in pan-cancer analysis. Remarkably, our model, upon rigorous validation, outperformed 16 pre-existing counterparts, offering a promising avenue for prognosis prediction. The risk score was used to classify patients into high and low-risk subgroups. The low-risk group showed improved overall survival (OS) and progression-free survival (PFS). The risk score was proved to be an independent prognosis factor. The low-risk group patients also exhibited a higher immune infiltration score and homologous recombination deficiency (HRD) score. Moreover, consensus clustering analysis was utilized to categorize OC patients into three distinct groups, predicated on the expression of the five prognostic lncRNAs. Patients within the third cluster exhibited noteworthy traits, encompassing elevated survival, heightened immune checkpoint expression, and the HRD score. Finally, the expressions of five PRlncRNAs were validated by quantitative real-time PCR (qRT-PCR) in OC cell lines and tissues. In conclusion, the risk model based on the five PRlncRNAs might function as prognostic biomarkers to predict the immune and target drug treatment in OC.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00173-x.

Mobile health technologies provided innovative solutions for lifestyle interventions and offered reliable methods to evaluate behavioral phenotypes during such interventions. To systematically quantify the impacts of behavioral compliance on weight-loss and metabolic profiles during lifestyle intervention, a total of 395 Chinese adults with overweight/obesity (BMI ≥ 24 kg/m²) or central obesity (waistline ≥ 90 cm for men or ≥ 80 cm for women) were randomly assigned to a smartphone app-based arm (SAA, n = 197) or smartphone app plus dietitian arm (SADA, n = 198) for 6 months. Compliance scores (0-5) were determined based on fulfilling five behavioral tasks: completing online courses, wearing a smart band, and recording weight, food intake, and blood pressure. SADA had greater weight-loss (- 4.94% vs. - 2.28%, p < 0.001) and lower triglyceride, but higher HDL-C levels (both p < 0.05) than SAA after six months. Between-group weight-loss differences were attenuated at compliance scores ≥ 3 (SADA: - 6.30% vs. SAA: - 4.79%, p = 0.07). Mediation analysis suggested that compliance scores explained approximately 30% of the additional weight loss in the SADA (p < 0.001), and self-weighing was the primary mediator (p < 0.05). Higher educational levels, greater initial weight loss, self-perceived simplicity, and satisfaction with the program were potential determinants of intervention compliance. Overall, the superior weight loss and metabolic improvements in the SADA group could be mediated by behavioral compliance, which was possibly influenced by some demographic and intervention response features. Our findings highlighted the roles of behavioral phenotypes and adherence in app-based lifestyle interventions, and added evidence for the future development of more precise strategies in long-term weight management.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00162-0.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and immune checkpoint inhibitor (ICI)-based therapies are now an integral part of systemic treatment. In this study, we identify potential biomarker for HCC and further investigate its functional significance using both bioinformatic and experimental methods. Differential analysis and weighted gene co-expression network analysis (WGCNA) were conducted, identifying lumican (LUM) as the target gene. Our results showed a significant downregulation of LUM in HCC. LUM expression was also associated with the progression-free interval and the infiltration of B cells, neutrophils, and myeloid dendritic cells. Enrichment analysis highlighted the involvement of LUM in focal adhesion and the extracellular matrix. In addition, overexpression of LUM suppressed proliferation, migration and invasion in hepatoma cell lines while promoting cell apoptosis. Our results demonstrate the importance of LUM in HCC development and may help to elucidate the underlying mechanisms and biological processes influenced by LUM.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00182-w.

This cross-sectional study aimed to investigate the corneal endothelial characteristics in elderly individuals with high myopia. We assessed corneal endothelial characteristics in 1065 eyes of 1065 elderly patients (549 highly myopic and 516 control eyes) using non-contact specular microscopy. Confirmation of suspected Fuchs endothelial corneal dystrophy (FECD) was performed with slit-lamp and confocal microscopy. Highly myopic eyes exhibited significantly greater central endothelial cell density (ECD) and coefficient of variation (CV) (p = 0.001 and p = 0.002, respectively), and lower average cell area (AVG) and percent of hexagonality (HEX) (p = 0.014 and p < 0.001, respectively) compared to control eyes. After adjusting for age and gender, axial length (AL) was positively correlated with ECD and CV (r = 0.130, p < 0.001 and r = 0.113, p < 0.001, respectively), and was negatively correlated with AVG and HEX (r = - 0.105, p = 0.001 and r = - 0.204, p < 0.001, respectively). FECD prevalence was 4.92% in highly myopic eyes and 3.29% in controls, with more advanced cases in highly myopic eyes (p = 0.036). In conclusion, longer AL was associated with increased corneal ECD, and greater endothelial pleomorphism and polymegethism in elderly patients. Highly myopic eyes appeared to have higher prevalence and severity of FECD. The study was registered on www.clinicaltrials.gov on February 26, 2017, with the registration number NCT03062085.

Compared with the well-documented inverse comorbidity of common neurodegenerative diseases with some types of cancer, the association of amyotrophic lateral sclerosis (ALS) with cancer was obscure. This Mendelian randomization (MR) analysis was aimed to appraise the causal relationship of ALS with cancer. Leveraging summary statistics of genome-wide association study (GWAS) for ALS, overall-cancer and nine types of site-specific common solid cancer including colorectal cancer (CRC) in populations of European (discovery and replication) and East Asian ancestry, we investigated the causal association of ALS with cancer using inverse-variance weighted (IVW) method and complementary sensitivity analyses. We performed MR-based mediation analysis to assess possible role of serum lipid traits such as hyperlipidemia, one shared risk factor of ALS and CRC, in their causal association. We found that genetically-predicted ALS was not associated with overall-cancer and other tested types of cancer, but was causally associated with reduced risk of CRC [odds ratio (OR) 0.84; 95% confidence interval (95% CI) 0.74-0.96; p = 0.011, OR 0.32; 95% CI 0.15-0.69; p = 0.004, in datasets of European (discovery) and East Asian ancestry respectively]. We observed absences of directional pleiotropy (MR Egger, intercept = -0.02 and -0.02, p = 0.49 and 0.60), instrumental outlier (MR-PRESSO, p = 0.95 and 0.84) or heterogeneity (Cochran Q, p = 0.95 and 0.82). Null reverse causality of CRC with ALS was found in either datasets. However, we found no evidence of the inverse association of ALS with CRC in either the replication (OR 0.99; 95% CI 0.93-1.06) or the combined European datasets (OR 0.92; 95% CI 0.79-1.09). Mediation analysis in European datasets suggested that hyperlipidemia may affect the risk of CRC via ALS in an indirect manner, with the measured mediation effect of hyperlipidemia on CRC being -0.02 (95% CI -0.04 to -0.002, p = 0.03). Our two-sample MR study in trans-ethnic populations uncovered that genetically proxied ALS may be causally associated with reduced risk of CRC, providing new insight into the inverse comorbidity and etiological causality of neurodegenerative disease and cancer.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00159-9.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation. While a few susceptibility genes for TOF have been identified, research on the genetic basis of TOF is limited. The Macrophage stimulating 1 receptor (MST1R) gene encodes the macrophage-stimulating protein receptor with tyrosine phosphatase activity that is involved in immune defense. In this study, we performed whole-exome sequencing (WES) on 10 TOF families and 50 sporadic TOF patients and identified a recessive homozygous missense mutation in MST1R, c.T2009G: p.V670G, in two offspring with TOF in a single family. Targeted sequencing of the MST1R gene showed enrichment for rare variants in 417 TOF patients compared with East Asians in Genome Aggregation Database Version 2 (gnomADv2_EAS). MST1R-deficient human induced pluripotent stem cells (hiPSCs) maintained normal pluripotency but differentiated into non-functional cardiomyocytes (CMs). Taken together, our findings indicate that MST1R may play a critical role in cardiac differentiation and genetic variations in MST1R may be associated with the pathogenesis of TOF.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00175-9.