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肥胖的遗传原因:规划前进的道路。

Genetic causes of obesity: mapping a path forward.

作者信息

Loos Ruth J F

机构信息

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Trends Mol Med. 2025 Apr;31(4):319-325. doi: 10.1016/j.molmed.2025.02.002. Epub 2025 Mar 14.

Abstract

Over the past 30 years, significant progress has been made in understanding the genetic causes of obesity. In the coming years, catalogs that map each genetic variant to its genomic function are expected to accelerate variant-to-function (V2F) translation. Given that obesity is a heterogeneous disease, research will have to move beyond body mass index (BMI). Gene discovery efforts for more refined adiposity traits are poised to reveal additional genetic loci, pointing to new biological mechanisms. Obesity genetics research is reaching unprecedented heights and, along with a renewed interest in the development of weight-loss medication, it holds the potential to identify new drug targets. Polygenic scores (PGSs) that predict obesity risk are expected to further improve and will be particularly valuable early in life for timely prevention.

摘要

在过去30年里,在了解肥胖的遗传原因方面取得了重大进展。在未来几年,将每个基因变异与其基因组功能进行映射的目录有望加速变异到功能(V2F)的转化。鉴于肥胖是一种异质性疾病,研究将不得不超越体重指数(BMI)。针对更精确肥胖特征的基因发现工作有望揭示更多的基因位点,指向新的生物学机制。肥胖遗传学研究正达到前所未有的高度,并且随着对减肥药物开发的重新关注,它有潜力识别新的药物靶点。预测肥胖风险的多基因评分(PGS)有望进一步改进,并且在生命早期对于及时预防将特别有价值。

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