Dataset Information

Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.

ABSTRACT: Although the importance of inflammation in atherosclerosis is now well established, the exact molecular processes linking inflammation to the development and course of the disease are not sufficiently understood. In this context, modern genetics-as applied by genome-wide association studies (GWAS)-can serve as a comprehensive and unbiased tool for the screening of potentially involved pathways. Indeed, a considerable proportion of loci discovered by GWAS is assumed to affect inflammatory processes. Despite many well-replicated association findings, however, translating genomic hits to specific molecular mechanisms remains challenging. This review provides an overview of the currently most relevant inflammation-related GWAS findings in coronary artery disease and explores their potential clinical perspectives.

SUBMITTER: Mauersberger C

PROVIDER: S-EPMC7921935 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.

Mauersberger Carina C Schunkert Heribert H Sager Hendrik B HB

Cells 20210219 2

Although the importance of inflammation in atherosclerosis is now well established, the exact molecular processes linking inflammation to the development and course of the disease are not sufficiently understood. In this context, modern genetics-as applied by genome-wide association studies (GWAS)-can serve as a comprehensive and unbiased tool for the screening of potentially involved pathways. Indeed, a considerable proportion of loci discovered by GWAS is assumed to affect inflammatory process ...[more]

PMID: 33669721

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Project description:BackgroundAlzheimer's disease is a debilitating and highly heritable neurological condition. As such, genetic studies have sought to understand the genetic architecture of Alzheimer's disease since the 1990s, with successively larger genome-wide association studies (GWAS) and meta-analyses. These studies started with a small sample size of 1086 individuals in 2007, which was able to identify only the APOE locus. In 2013, the International Genomics of Alzheimer's Project (IGAP) did a meta-analysis of all existing GWAS using data from 74 046 individuals, which stood as the largest Alzheimer's disease GWAS until 2018. This meta-analysis discovered 19 susceptibility loci for Alzheimer's disease in populations of European ancestry.Recent developmentsThree new Alzheimer's disease GWAS published in 2018 and 2019, which used larger sample sizes and proxy phenotypes from biobanks, have substantially increased the number of known susceptibility loci in Alzheimer's disease to 40. The first, an updated GWAS from IGAP, included 94 437 individuals and discovered 24 susceptibility loci. Although IGAP sought to increase sample size by recruiting additional clinical cases and controls, the two other studies used parental family history of Alzheimer's disease to define proxy cases and controls in the UK Biobank for a genome-wide association by proxy, which was meta-analysed with data from GWAS of clinical Alzheimer's disease to attain sample sizes of 388 324 and 534 403 individuals. These two studies identified 27 and 29 susceptibility loci, respectively. However, the three studies were not independent because of the large overlap in their participants, and interpretation can be challenging because different variants and genes were highlighted by each study, even in the same locus. Furthermore, neither the variant with the strongest Alzheimer's disease association nor the nearest gene are necessarily causal. This situation presents difficulties for experimental studies, drug development, and other future research. WHERE NEXT?: The ultimate goal of understanding the genetic architecture of Alzheimer's disease is to characterise novel biological pathways that underly Alzheimer's disease pathogenesis and to identify novel drug targets. GWAS have successfully contributed to the characterisation of the genetic architecture of Alzheimer's disease, with the identification of 40 susceptibility loci; however, this does not equate to the discovery of 40 Alzheimer's disease genes. To identify Alzheimer's disease genes, these loci need to be mapped to variants and genes through functional genomics studies that combine annotation of variants, gene expression, and gene-based or pathway-based analyses. Such studies are ongoing and have validated several genes at Alzheimer's disease loci, but greater sample sizes and cell-type specific data are needed to map all GWAS loci.

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Dataset Information

Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.

Publications

Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.

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