Gene-Smoking Interaction in Insulin Sensitivity and β-Cell Function Among Normal Glucose Tolerance Individuals.

Objective: To identify genetic loci that exhibit potential interactions with smoking status on insulin sensitivity and islet β-cell function within normal glucose tolerance (NGT) populations.

Methods: All participants underwent an OGTT to confirm NGT status, followed by assessments of insulin sensitivity and β-cell function. Analyses were performed in NGT participants from Nanjing (N = 4808) and Jurong (N = 508) for discovery and validation, respectively.

Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes.

C-reactive protein (CRP) serves as a pivotal marker of systemic inflammation, yet its genetic architecture has predominantly been explored within European populations. Our multi-ancestry sequencing-based genome-wide association study (seqGWAS) meta-analysis encompasses 447,369 Europeans, 10,389 Africans, 9685 Asians, and 9200 Hispanics in the discovery set, and 23,521 Europeans, 7160 Africans, 771 Asians, and 5178 Hispanics in the replication set. We identify 113 independent association signals (P ≤ 5 × 10 and P ≤ 0.

Investigating the common genetic architecture and causality of metabolic disorders with neurodegenerative diseases.

Background: The co-occurrence of metabolic dysfunction and neurodegenerative diseases suggests a genetic link, yet the shared genetic architecture and causality remain unclear. We aimed to comprehensively characterise these genetic relationships.

Methods: We investigated genetic correlations among four neurodegenerative diseases and seven metabolic dysfunctions, followed by bidirectional Mendelian randomisation (MR) to assess potential causal relationships.

Proteome-wide Mendelian randomization identifies causal plasma proteins in lung cancer.

Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank.