Biomedical subjects

Liming Li

Publications and source records attributed to Liming Li.

5 recordsLinked to original sources

PubMed2026

Incidence patterns and genetic validation of primary glaucoma subtypes among 1 million adults in China and the UK.

BACKGROUND/AIMS: Primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) are distinct diseases, yet many glaucoma cases in population-based datasets lack subtype specification. We assessed incidence patterns of glaucoma subtypes in China and the UK and used genetic evidence to infer the likely subtype composition of cases recorded as unspecified glaucoma. METHODS: Incident primary glaucoma was identified from linked inpatient records in the prospective China Kadoorie Biobank (CKB; n=512 504) and UK Biobank (UKB; n=492 329) studies. Cohort-specific phenotyping algorithms defined POAG, PACG and unspecified glaucoma. Adjusted incidence rates were estimated by direct standardisation. To support subtype inference, polygenic risk scores (PRSs) were constructed using ancestry-specific genome-wide association studies, including a new East Asian PACG meta-analysis, and tested for association with glaucoma phenotypes using multivariable logistic regression. RESULTS: Over 12 years of follow-up, 1658 primary glaucoma cases were identified in CKB and 7643 in UKB. Most (>68%) cases lacked subtype specification. Incidence increased with age and was twofold higher among women for PACG in both cohorts and for unspecified glaucoma in CKB. In UKB, POAG incidence was fivefold higher among Black than White participants, with a similar but attenuated pattern for unspecified glaucoma. PRS analyses indicated that unspecified glaucoma closely aligned with PACG in CKB but was more heterogeneous in UKB. CONCLUSION: Healthcare-recorded incidence patterns for POAG and PACG were consistent with established demographic risk factors, whereas unspecified glaucoma showed differences in subtype composition between populations. Integrating epidemiological and genetic evidence improves interpretation of glaucoma phenotypes when detailed clinical information is unavailable.

Epidemiology↗

PubMed2026

Exploring China's Clean Air Act and associated cardiovascular disease risk: a prospective, quasi-experimental, and causal inference modelling study.

BACKGROUND: Substantial improvements in air quality have been recorded following the implementation of China's Clean Air Act (CCAA) in 2013. However, the association between CCAA implementation and individual-level cardiovascular disease (CVD) risk remains unclear. We aimed to examine the long-term association between CCAA implementation and individual-level predicted CVD risk. METHODS: In this prospective, quasi-experimental study, we used data from the China Kadoorie Biobank, a prospective cohort study that recruited participants from five urban and five rural areas across China between 2004 and 2008, with three resurveys conducted after the baseline survey (in 2008, 2013-14, and 2020-21). We included 34 862 individuals (mean age 51·3 years) who participated in at least one resurvey and had no history of CVD at baseline. Participants were classified into intervention (n=25 497) and control (n=9365) groups based on the local government's targets for particulate matter reduction. We estimated the 10-year risk of incident CVD morbidity or mortality using a validated risk prediction model. We used a difference-in-difference model to assess the long-term association between CCAA implementation and predicted risk, with adjustments made for regional confounders and individual-level characteristics, including demographics, lifestyle factors, medical history, and indoor air pollution exposure. The relationship between changes in long-term exposure to PM2·5, PM10, and O3 and predicted risk after CCAA implementation was analysed using a linear model. The estimated risk differences associated with air pollutant changes were estimated based on the magnitude of changes and their corresponding effect sizes. FINDINGS: After the CCAA was implemented, PM2·5 and PM10 concentrations declined in both groups, but O3 concentrations increased. The intervention group showed a 3·95% (95% CI 3·18-4·72%) lower increase in predicted risk than the control group, with larger estimated differences under stricter enforcement. Between 2013 and 2021, each 10 μg/m3 change in PM2·5 concentration was positively associated with a 1·80 (1·34-2·27) percentage point change in predicted CVD risk, whereas each 10 μg/m3 change in PM10 concentration was associated with a 1·24 (0·84-1·63) percentage point change and each 10 μg/m3 change in O3 concentration with a 0·58 (0·33-0·83) percentage point change. Overall, the observed changes in air pollutants during the study period were associated with an average 6·6 percentage point reduction in predicted CVD risk. INTERPRETATION: The CCAA and improved air quality were associated with a slower increase in predicted CVD risk, supporting the necessity for stricter, multipollutant air quality policies to maximise public health benefits. FUNDING: National Natural Science Foundation of China, Kadoorie Charitable Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, Chinese Ministry of Science and Technology, and UK Wellcome Trust.

Journal Article↗

PubMed2026

Cross-Ancestry Proteogenomic Analyses Identified New Therapeutic Insights for Ischemic Heart Disease.

BACKGROUND: Most drugs target proteins, and proteome-wide genetic analyses in diverse populations could discover potential novel and repurposed targets for improved prevention and treatment of ischemic heart disease (IHD) beyond statin therapy. OBJECTIVES: The purposes of this study were to use cis-acting single nucleotide polymorphisms (cis-pQTLs) identified for plasma proteins in East Asians and Europeans to discover and validate potential drug targets for IHD. METHODS: We measured plasma levels of 9,520 (Olink/SomaScan: 2,923/7,297) proteins in a case-cohort study of IHD (1,976 incident cases and 2,001 subcohort controls) in statin-free individuals in the prospective China Kadoorie Biobank (CKB). Genome-wide association studies identified 2,895 (Olink/SomaScan: 1,301/1,594) cis-pQTLs for these proteins in CKB. Two-sample Mendelian randomization (MR) and colocalization analyses assessed associations of all available cis-pQTLs for these proteins with IHD in East Asians (n = 29,319 cases), with further replication in Europeans (n = 181,522 cases) and comparison with findings in previous MR studies. RESULTS: In CKB observational analyses, a total of 959 (Olink/SomaScan: 426/533) proteins were associated at false discovery rate-corrected P < 0.05 with IHD after adjusting for major IHD risk factors. Two-sample MR analyses provided genetic support for 54 unique (Olink/SomaScan: 36/28) proteins in IHD etiology. Colocalization analyses confirmed shared gene-protein-IHD associations (posterior probability of hypothesis 4 [PPH4] ≥0.8) for 15 unique (Olink/SomaScan: 10/10) proteins, including 8 lipid-related, 3 inflammation-related, 1 blood pressure-related, and 3 alcohol-related proteins in East Asians. In Europeans, MR analyses of 12 non-alcohol-related proteins showed directionally concordant results for 8 proteins, with 5 having strong colocalization evidence of shared gene-protein-IHD associations (PPH4 ≥0.8), including 4 lipid-related (proprotein convertase subtilisin/kexin type 9, LPA, APOE, cadherin-1) and 1 systolic blood pressure-related (fibroblast growth factor 5) protein. However, 4 proteins showed directionally discordant MR results, including 2 lipid-related (APOA5, SORT1) and 1 inflammation-related (transforming growth factor beta 1) proteins with strong colocalization evidence of shared gene-protein-IHD associations (PPH4 ≥0.8). Comparison with previous MR studies revealed little consistency across studies in the number and identity of target proteins for IHD beyond well-established lipid-related (low-density lipoprotein cholesterol, lipoprotein(a), and triglycerides) or inflammation-related (interleukin-6) protein targets. CONCLUSIONS: The findings support a role for lipid-driven chronic inflammation in IHD etiology, and treatment strategies simultaneously targeting multiple lipid and inflammation pathways should be prioritized for further research to improve drug treatment of IHD beyond statin therapy.

Aged↗

PubMed2026

Plasma signals of lung tumor promotion for molecular cancer prevention.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Humans↗

PubMed2022

Temporal associations between leukocytes DNA methylation and blood lipids: a longitudinal study.

BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450 K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.

Humans↗