Strategies for identifying the genetic basis of dyslipidemia: genome-wide association studies vs. the resequencing of extremes

Current Opinion in Lipidology
Chiea Chuen Khor, Denise Li-Meng Goh

Abstract

Genome-wide association studies (GWASs) and the resequencing of extremes are two methods currently being used to identify the causative variants in dyslipidemia. GWASs are high-throughput, array-based platforms. They are nonhypothesis-based and scan within and across many genes. Associated variants identified via GWAS are likely to be common, have modest effect sizes, and are more likely to be a disease marker rather than the true causative variant. Currently, GWAS-identified variants explain only a small amount of heritability associated with dyslipidemia. Resequencing of extremes involves deep sequencing of two groups of individuals, one at each extreme of the phenotype. It is usually used to evaluate genomic regions with a high prior index of suspicion (e.g. genes underlying strong linkage peaks). The associations detected are more likely to reflect causative variants of larger effect size than GWAS-identified variants. The proportion of heritability associated with dyslipidemia explained by rare variants is currently unknown. Both methods have identified variants that are associated with dyslipidemia and will continue to be used as they play complementary roles.

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Citations

May 3, 2011·Breast Cancer Research and Treatment·Julie JohnsonGeorgia Chenevix-Trench
Aug 6, 2011·European Journal of Pharmacology·Amy L InselmanJim Kaput
May 22, 2016·Journal of Clinical Lipidology·Weerapan KhovidhunkitWanee Plengpanich
Nov 29, 2011·Journal of Periodontal Research·L ChaiW K Leung
Apr 27, 2011·Current Opinion in Lipidology·Christopher T Johansen, Robert A Hegele
Mar 2, 2021·Chinese Journal of Natural Medicines·Qi RenXian-Tao Li

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