Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University, New York, New York, USA.
Curr Opin Lipidol. 2019 Jun;30(3):157-164. doi: 10.1097/MOL.0000000000000605.
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 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.
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.
残余心血管疾病风险和代谢综合征风险增加，凸显了人类需要针对脂质代谢的新型治疗方法。无偏倚的人类遗传筛选已被证明在识别新的基因组座方面非常有效，本综述讨论了这一发现的最新进展。
最近已经在规模庞大、详细的队列中完成了全人类基因组关联研究，确定了 300 多个参与调节血浆脂质代谢的基因组座。然而，这些座的发现远远超过了对潜在功能机制的阐明。长非编码 RNA（如 CHROME、LeXis 和 MeXis）在脂质代谢中发挥新作用的鉴定表明，非编码 RNA 应包括在 GWAS 座的功能翻译中。
无偏遗传研究似乎在脂质代谢方面揭示了大量新的生物学信息，但将这些发现转化为可行的机制的速度较慢。增加对这些基因座的翻译（而不是发现）的关注，同时关注 lncRNA，可以帮助推动针对脂质代谢的新型治疗方法的发展。
