Biomedical subjects

Wen Luo

Publications and source records attributed to Wen Luo.

4 recordsLinked to original sources

PubMed2026

Standard tea intake is causally associated with a reduced risk of wet age-related macular degeneration: a Mendelian randomization study.

Researchers have posited that increased consumption of tea and coffee may be associated with more favorable treatment outcomes in patients with age-related macular degeneration (AMD). However, there is no clear evidence regarding the causal associations. To delve deeper into this potential connection, scientists used a rigorous method known as Mendelian randomization (MR). This technique was used to explore the causal impact of tea and coffee consumption on the development or progression of AMD. With the aim of investigating the cause-and-effect relationship between 16 tea- and coffee-consuming subtypes and 3 AMD, we designed a two-sample MR study using comprehensive data from genome-wide association studies (GWAS). The major approach adopted was inverse variance weighting (IVW). Furthermore, we implemented complementary methods like the weighted median (WM), weighted mode, and MR-Egger to strengthen our findings. Sensitivity analyses, including MR-Egger, MR-PRESSO, leave-one-out, and Cochran's Q tests, were used to validate results, explore heterogeneity and pleiotropy, and pinpoint potential biases. Two hundred and sixty-eight instrumental variables were selected for MR analysis. The results showed that standard tea intake may be a protective factor for wet AMD [odds ratio (OR) = 0.7076, 95% confidence interval (CI) = 0.5776-0.8668, P = 8 × 10-4, PFDR = 0.0402]. Sensitivity analysis suggests that the results are robust. Our findings provide genetic evidence that standard tea intake is a protective factor against wet AMD, providing new insights into early risk stratification and prevention strategies for the disease.NEW & NOTEWORTHY This study investigates the potential causal relationship between tea and coffee consumption and age-related macular degeneration (AMD) using Mendelian randomization. Analyzing data from genome-wide association studies, we focused on 16 beverage subtypes and 3 AMD conditions. Our findings suggest that standard tea consumption may protect against wet AMD, with robust evidence supporting this link. The results offer new insights into risk stratification and prevention strategies for AMD, highlighting the importance of dietary factors in eye health.

Mendelian Randomization Analysis↗

PubMed2026

Discovery of a potential novel pharmacogenomic biomarker on ANK3 gene for liafensine, a triple reuptake inhibitor for treatment-resistant depression.

Liafensine is a triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine for treatment-resistant depression (TRD). It did not exhibit efficacy in non-biomarker-selected TRD patients in two Phase 2b studies. We utilized the blood samples from the patients enrolled in these two studies and extracted genomic DNA to conduct a genome‑wide association study aiming to find a biomarker which can predict liafensine response. A single single-nucleotide polymorphism (SNP), rs12217173, at ANK3 gene was identified as strongly associated with treatment response to liafensine (p = 6.61 × 10-8) in the discovery set (n = 186) and was further confirmed in the replication sample set (n = 47, p = 0.05, combined p = 1.27 × 10-8). In addition, this SNP was not associated with the efficacy of the duloxetine or escitalopram, suggesting it is a liafensine-specific biomarker. This finding was subsequently confirmed in a prospective clinical study. Thus, this study represents a novel approach to translating precision medicine into psychiatric diseases.

Humans↗

PubMed2026

Disruption of CTCF binding by germline non-coding variants in CDKN2B suppress CDKN2A expression and predispose to melanoma.

Some melanoma-prone families linked to the 9p21 locus, harboring the established susceptibility gene CDKN2A, lack pathogenic protein-coding variants. Using whole-exome and targeted sequencing, we identified three rare single-nucleotide variants in two melanoma-prone families and one sporadic melanoma case. Variants map to a conserved CTCF-bound region within the first intron of CDKN2B that physically interacts with CDKN2A. Analysis of UK Biobank showed significant enrichment of variants in this region in melanoma cases. Variants result in diminished CTCF binding in vitro. CTCF ChIP-seq in fibroblasts from the carriers of the largest family demonstrated loss of CTCF binding, accompanied by weakened promoter interactions and allele-specific reduction of CDKN2A p16 transcript expression from the variant haplotype. CRISPR-based perturbation of this region and editing of the large family variant into melanocytes resulted in reduced expression of p14 and p16 CDKN2A transcripts. These findings suggest that non-coding regulatory variants function as high-penetrance susceptibility alleles in melanoma families by altering CDKN2A function.

Journal Article↗

PubMed2026

STK11 Mutations and Deletions Define an Aggressive Molecular Subgroup of Cervical Adenocarcinoma.

Cervical adenocarcinoma accounts for 15%-20% of cervical cancers and is associated with poorer survival and reduced response to screening and immunotherapy compared with squamous cell carcinoma (SCC). The genomic drivers underlying this molecular subgroup remain incompletely characterized. Whole-exome sequencing was performed on 302 invasive cervical cancers from Guatemala and Venezuela. Structural variation analysis was conducted using SNP-array and whole-genome sequencing data. Findings were replicated in more than 4600 additional cervical cancer samples from TCGA, AACR Project GENIE, MSKCC, and Caris datasets. TP53 mutations were more frequent in adenocarcinoma than SCC, particularly in HPV-negative tumors. STK11 alterations, including mutations and focal deletions, were significantly enriched in HPV-positive adenocarcinomas compared with SCC and affected 23% of adenocarcinomas overall. Whole-genome analyses identified recurrent focal deletions, inversions, chromosomal rearrangements, and breakage-fusion-bridge events involving chromosome 19p and STK11 that were not detected by exome sequencing alone. STK11 alterations were associated with younger age at diagnosis, poorer overall survival, and inferior outcomes following immune checkpoint inhibitor (ICI) therapy. STK11 alterations significantly co-occurred with YAP1 amplification but were largely mutually exclusive with PIK3CA mutation. Cervical adenocarcinomas also demonstrated significantly lower CD274 (PD-L1) expression than SCC. STK11 alterations define a distinct molecular subgroup of cervical adenocarcinoma characterized by structural disruption of chromosome 19p, younger age at onset, and poorer clinical outcomes. These findings have implications for molecular classification and future targeted therapeutic approaches in cervical cancer.

Humans↗