Additional file 1. Table S1: “Summary of the studies in the meta-analysis for the association between Season of Birth and DNA methylation at birth and in children (age: 1 to 11 years)”. Baseline summary of participants from each of the individual cohorts.
Abstract Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes.
To identify cell specific molecular changes associated with sarcoidosis risk and progression, we aimed to characterize the cellular composition, gene expression patterns, and cell-cell interactions in BAL cells from patients with sarcoidosis (both progressive and non-progressive) and healthy controls. Single cell RNA-seq data were collected on 12 sarcoidosis and 4 control participants. We combined scRNA-seq data from these participants with our previously collected data on 4 sarcoidosis and 10 control participants for a final sample size of 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls. Following initial preprocessing in CellRanger, data were quality controlled, combined, and clustered in Seurat. We tested differences in cell proportions by disease group using F-tests on cell proportions and differences in gene expression using pseudobulk analysis. Cell to cell communication and pathway analysis were performed using CellChat. We identified five macrophage populations: resident, high metallothionein (MT) resident, recruited, profibrotic recruited, and proliferating macrophages. Each subpopulation displayed unique gene expression profiles, with notable differential expression of genes and pathways linked to sarcoidosis in resident macrophages, recruited macrophages, and proliferating macrophages. We also observed changes in gene expression associated with disease progression in resident and recruited macrophages. In non-macrophages cells, we observed a significant reduction in the number of B cells in sarcoidosis patients compared to controls. Among T cell populations, we identified specific transcriptional alterations at gene and pathway level. Additionally, we observed distinct differences in cell-to-cell interactions of macrophages and T cells between sarcoidosis patients and healthy controls. These findings underscore the complexity of immune cell involvement in sarcoidosis and highlight potential cellular and molecular targets for further investigation.
