Biomedical subjects

Mikyeong Lee

Publications and source records attributed to Mikyeong Lee.

3 recordsLinked to original sources

PubMed2026

Proteome-wide Mendelian randomisation of lung function to identify potential therapeutic targets for respiratory disease.

BACKGROUND: Despite multiple clinical trials, disease-modifying treatments for COPD are currently limited. Since many drugs target proteins, identifying causality between proteins and lung function informs understanding of COPD pathophysiology and may suggest novel targets. We used Mendelian randomisation (MR) to prioritise proteins as potentially causal for imparied lung function. For prioritised proteins, we explored their potential suitability as drug targets by predicting their effects on a range of clinical outcomes. METHODS: We used genome-wide association study (GWAS) data on 2923 proteins (n=48 195, UK Biobank) to identify single genetic variants (protein quantitative trait loci (cis-pQTLs)) associated with protein levels (p≤5×10-9, variant ≤100 kb of a transcription start site). We performed cis-pQTL-MR analyses of four spirometric traits (n=149 166, 36 independent cohorts). Sensitivity analyses included colocalisation and reverse direction MR. We report associations between cis-pQTLs for prioritised proteins and multiple clinical respiratory outcomes, and use phenome-wide analysis to explore potential adverse effects or drug repurposing opportunities. FINDINGS: 1841 proteins had a suitable cis-pQTL. We implicated 16 proteins as potentially causal for lung function (p<1.71×10-5): seven proteins have not been implicated by previous lung function GWAS or MR (CCND2, DTD1, PILRA, PTPRK, TDRKH, GRHPR, NUDT5), and we provide corroborative evidence for 10 proteins. We add to the literature identifying surfactant protein D (SFTPD) as a candidate, yet predict that integrin subunit alpha V (ITGAV) inhibition could impair some lung function measures, mimicking adverse results from a recent trial. INTERPRETATION: Our approach identifies proteins (some novel) that are potentially therapeutic targets for respiratory disease, and which warrant follow-up for utility and safety.

Journal Article↗

PubMed2025

Animal farming and the oral microbiome in the Agricultural Health Study.

BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study. METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption). RESULTS: Overall, 63 % of participants raised farm animals, most commonly cattle (46 %) and hogs (20 %). Those who raised a large number of hogs (≥2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry). CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.

Microbiota↗

PubMed2024

Association analysis between an epigenetic alcohol risk score and blood pressure.

BACKGROUND: Epigenome-wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. RESULTS: We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p < 0.0001). We examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with BP levels, i.e., a one-unit increase in ERS was associated with 0.74 mm Hg (p = 0.002) higher SBP and 0.50 mm Hg (p = 0.0006) higher DBP, but not with HTN. Longitudinal analyses in FHS (n = 3260) and five independent external cohorts (n = 4021) showed that the baseline ERS was not associated with a change in BP over time or with incident HTN. CONCLUSIONS: Our findings demonstrate that the ERS has potential clinical utility in assessing lifestyle factors related to cardiovascular risk, especially when self-reported behavioral data (e.g., alcohol consumption) are unreliable or unavailable.

Humans↗