Advanced Search

Submit Manuscript

Volume 30, No 4, Apr 2020

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 30 Issue 4, April 2020: 363-365

LETTERS TO THE EDITOR

Hypercholesterolemia risk-associated GPR146 is an orphan G-protein coupled receptor that regulates blood cholesterol levels in humans and mice

Fangfang Han1 , Xiao Liu1 , Chuanfang Chen1 , Yinan Liu1 , Mingkun Du1 , Yu Zhou1 , Yong Liu1 , Bao-Liang Song1 , Housheng Hansen He2,3 , Yan Wang1,*

1Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, 430072 Wuhan, Hubei, China
2Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada
3Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 3G3, Canada
These authors contributed equally: Fangfang Han, Xiao Liu, Chuanfang Chen, Yinan Liu Correspondence: Yan Wang(Wang.y@whu.edu.cn)

Dear Editor,

Hypercholesterolemia is the leading risk factor for cardiovascular diseases. Current evidence suggests that the heritability for blood cholesterol levels is high, with 40%–60% in different cohorts.1,2 Genome-wide association study (GWAS) is a powerful tool to ascertain the contribution of common genetic variants in population-wide disease variability. It has been performed extensively on blood lipids traits and hundreds of genome variants are associated with dyslipidemia. However, approximately 95% of these variants are located in genome noncoding regions and cluster in more than 300 loci in different populations.3 We find that approximately 2/3 of these loci are located in noncoding regions and are not close to any gene that known plays a role in lipid metabolism. The disease-causing variants in these loci and the molecular mechanisms remain largely unknown, which prevents the interpretation of the GWAS results and their application in precision medicine. On the other hand, these noncoding regions may harbor novel genes or signaling pathways involved in lipid metabolism and be a valuable resource for further mechanistic studies.



https://doi.org/10.1038/s41422-020-0303-z

FULL TEXT | PDF

Browse 726