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- W2526907187 abstract "Despite the development of genomic research on common cardiovascular diseases, genetic variants and/or loci shown to be disease associated have been seldom applied to risk prediction in a clinical setting, although they could provide us with novel mechanistic insights into the pathophysiology and potential therapeutic targets. Here, we discuss the significance and limitations of the up-to-date genomic studies on common diseases and propose what kind of genomic research should be prioritized in view of the realization of precision medicine. Many disease-associated loci have been identified using a genome-wide association study (GWAS) in a large-scale case–control design (more than several thousand cases and controls). A GWAS is an analytical method for the identification of disease-associated tag (lead) SNPs, which are indicators of disease-associated loci (linkage disequilibrium blocks) with a genome-wide significance ( P <5×10−8). Consequently, further analysis is required to identify the specific variants functioning as the most associated and/or risk variants1 within each disease-associated locus. Consistent with the genetic cause of monogenic diseases, novel biology on the risk genes and their regulatory pathways can be learned through detailed genetic and functional analysis after GWAS. Also, GWAS data on disease-associated pathways might be used in choosing drugs for treatment.2 We have experienced several successful stories. Single-nucleotide polymorphisms (SNPs) in PCSK9 , HMGCR , and NPC1L 1 were shown to be associated with hypercholesterolemia in GWAS on blood lipids.3 Although their effects shown in that GWAS were relatively weak (+2–3 mg/dL change in plasma cholesterol values), potent compounds targeting these gene-encoded proteins have been established as lipid-lowering agents (anti-PCSK9 antibody, statin, and ezetimibe, respectively). In this way, GWAS data can provide the scientific community with information about novel biology, mechanical pathways, and potential pharmaceutical drugs.Because current GWASs are usually performed with a case–control design, the results are …" @default.
- W2526907187 created "2016-10-07" @default.
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- W2526907187 date "2016-09-30" @default.
- W2526907187 modified "2023-09-30" @default.
- W2526907187 title "A Strategy for Genomic Research on Common Cardiovascular Diseases Aiming at the Realization of Precision Medicine" @default.
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- W2526907187 doi "https://doi.org/10.1161/circresaha.116.309802" @default.
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