대한신장학회

Skip Navigation: Skip to contents

KOR
ENG
전체메뉴보기

간행물 검색

현재 페이지 경로

HOME
간행물
간행물 검색

논문분류	춘계학술대회 초록집
제목	Proteome-wide Association Study Identifies Plasma Protein Signatures for Incident Acute Myocardial Infarction Across eGFR Strata in the UK Biobank
저자	Yongwoo Lee
출판정보	2026; 2026(1):
키워드	Proteomics, Acute myocardial infarction, Estimated glomerular filtration rate, UK Biobank, Machine learning
초록	Objectives: To identify plasma proteins associated with incident AMI across eGFR strata using a proteome-wide association study (PWAS), and to evaluate whether proteomic features improve AMI prediction in individuals with reduced eGFR. Methods: Among 31,436 UK Biobank participants with 2,923 plasma proteins (Olink Explore), Cox models were applied in three strata: overall cohort, reduced eGFR subgroup (eGFR <60; N=744), and sensitivity cohort (eGFR <75; N=3,719), adjusting for age, sex, BMI, eGFR, diabetes, hypertension, SBP, cholesterol, CRP, and smoking. FDR q<0.05 was applied overall; nominal p<0.05 in reduced eGFR strata. Pathway enrichment used clusterProfiler. Machine learning compared clinical-only (Model A) versus clinical plus LASSO-selected proteins (Model B). Results: Over 13.15 years median follow-up, 1,649 AMI events occurred. After full adjustment, 362 proteins were associated with AMI (FDR q<0.05), with cytokine-cytokine receptor interaction as the top KEGG pathway (59 genes, q=1.9×10⁻⁹). Sixteen proteins were significant across all eGFR strata, including EDA2R (HR 3.59), MMP12 (HR 1.87), IGFBP4 (HR 2.22), and EGFR (HR 0.22). Two dose-response patterns emerged: monotonically increasing HRs with declining eGFR (e.g., RBFOX3: HR 1.21 to 4.51 from eGFR ≥90 to 30–44), and non-monotonic trajectories peaking at eGFR 60–89. PLA2G7–AMI association was markedly attenuated at eGFR <60 (interaction HR 0.035, p=0.0009). Proteomic features improved AUC by 13.5% (0.691 to 0.783; validation AUC 0.798–0.835). Conclusion: This PWAS identifies 362 AMI-associated proteins and 16 cross-strata consensus biomarkers driven by cytokine signaling. eGFR-dependent dose-response patterns and PLA2G7 interaction offer mechanistic insights into cardiorenal risk. Proteomic profiling substantially improves AMI prediction beyond clinical variables in individuals with reduced kidney function.
원문(PDF)	PDF 원문보기

목록

위로가기