Dataset Information

Genetic association study of fatal pulmonary embolism.

ABSTRACT: Pulmonary embolism (PE) is a complex multi-factorial disease and represents one manifestation of venous thromboembolism (VTE). Most commonly PE constitutes a complication of VTE's other clinical presentation deep vein thrombosis (DVT). The majority of studies concerning risk factors do not distinguish between PE and DVT. The risk factors are often estimated to be alike, but the prevalence and the risk associated with the major genetic factor Factor V Leiden differ between the two disease states. We have investigated the association of 22 SNPs with PE in 185 PE case and 375 healthy control subjects. At p?=?0.05, eight SNPs presented with nominally significant evidence of association (EOA), although no significantly different genotype distributions remained between cases and controls after Bonferroni correction. Three of these variants (rs1800790, rs3813948, rs6025) showed EOA in the main analysis, and five variants (rs169713, rs1801131, rs4524, rs5985 and rs8176592) demonstrated EOAs in subgroups. Genomic variation modulating Factor V, Factor XIII, Beta fibrinogen (FGB), TFPI or HIVEP1 should be worth to be followed in subsequent studies. The findings of this study support the view that PE represents a complex disease with many factors contributing relatively small effects. Larger sample sizes will be required to reliably detect these small effects.

SUBMITTER: Meißner L

PROVIDER: S-EPMC7782449 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Genetic association study of fatal pulmonary embolism.

Meißner Lisa L Schürmann Peter P Dörk Thilo T Hagemeier Lars L Klintschar Michael M

International journal of legal medicine 20201030 1

Pulmonary embolism (PE) is a complex multi-factorial disease and represents one manifestation of venous thromboembolism (VTE). Most commonly PE constitutes a complication of VTE's other clinical presentation deep vein thrombosis (DVT). The majority of studies concerning risk factors do not distinguish between PE and DVT. The risk factors are often estimated to be alike, but the prevalence and the risk associated with the major genetic factor Factor V Leiden differ between the two disease states. ...[more]

PMID: 33128086

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Project description:BackgroundThe incidence of pulmonary embolism complications in the literature ranges from 10 to 50%, with a 0.5-10% risk of fatal pulmonary embolism. However, the biological cause of pulmonary embolism is unknown.MethodsThis study used data from the Genome-Wide Association Study (GWAS) of Pulmonary Embolism and Human Blood Metabolites from the UK Biobank, and the data from subjects of European ancestry were analyzed. We explored the relationship between pulmonary embolism and blood metabolites in three ways. We first analyzed the genetic correlation between pulmonary embolism and human blood metabolites using the linkage disequilibrium score regression (LDSC) and then analyzed the causal relationship between pulmonary embolism and meaningful blood metabolites obtained from the LDSC, a procedure for which we used Mendelian randomization analysis. Finally, we obtained transcriptome sequencing data for patients with a pulmonary embolism from the GEO database, analyzed differentially expressed genes (DEGs) in patients with pulmonary embolism versus healthy populations, and compared the DEGs with the resulting blood metabolite genes to further validate the relationship between pulmonary embolism and blood metabolites.ResultWe found six human blood metabolites genetically associated with pulmonary embolism, stearic acid glycerol phosphate ethanolamine (correlation coefficient = 0.2582, P = 0.0493), hydroxytryptophan (correlation coefficient = 0.2894, P = 0.0435), and N1-methyladenosine (correlation coefficient = 0.0439, P = 0.3728), and a significant causal relationship was discovered between hydroxytryptophan and pulmonary embolism. After screening microarray data from the GEO database, we performed differential gene analysis on the GSE19151 dataset and screened a total of 22,216 genes with P values less than 0.05, including 17,361 upregulated genes and 4854 downregulated genes. By comparing the resulting differentially expressed genes with six genes encoding blood metabolites, LIPC and NAT2 were found to be differentially expressed in association with pulmonary embolism.

Dataset Information

Genetic association study of fatal pulmonary embolism.

Publications

Genetic association study of fatal pulmonary embolism.

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