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Genetics-driven discovery of novel regulators of lipid metabolism

Ha, Elizabeth E.; Van Camp, Andrew G.; Bauer, Robert C.

Current Opinion in Lipidology: June 2019 - Volume 30 - Issue 3 - p 157–164
doi: 10.1097/MOL.0000000000000605
LIPID METABOLISM: Edited by Marit Westerterp and Bart van de Sluis
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Purpose of review Residual cardiovascular disease risk and increasing metabolic syndrome risk underscores a need for novel therapeutics targeting lipid metabolism in humans. Unbiased human genetic screens have proven powerful in identifying novel genomic loci, and this review discusses recent developments in such discovery.

Recent findings Recent human genome-wide association studies have been completed in incredibly large, detailed cohorts, allowing for the identification of more than 300 genomic loci that participate in the regulation of plasma lipid metabolism. However, the discovery of these loci has greatly outpaced the elucidation of the underlying functional mechanisms. The identification of novel roles for long noncoding RNAs, such as CHROME, LeXis, and MeXis, in lipid metabolism suggests that noncoding RNAs should be included in the functional translation of GWAS loci.

Summary Unbiased genetic studies appear to have unearthed a great deal of novel biology with respect to lipid metabolism, yet translation of these findings into actionable mechanisms has been slow. Increased focus on the translation, rather than the discovery, of these loci, with new attention paid to lncRNAs, can help spur the development of novel therapeutics targeting lipid metabolism.

Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University, New York, New York, USA

Correspondence to Robert C. Bauer, PhD, 630 W. 168th Street, PS10-401, New York, NY 10032, USA. E-mail: rcb36@columbia.edu

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