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Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Xu, Fengzhe 
Yu, Evan Yi-Wen 
Cai, Xue 
Yue, Liang 
Jing, Li-Peng 

Abstract

Identification of protein quantitative trait loci (pQTL) helps understand the underlying mechanisms of diseases and discover promising targets for pharmacological intervention. For most important class of drug targets, genetic evidence needs to be generalizable to diverse populations. Given that the majority of the previous studies were conducted in European ancestry populations, little is known about the protein-associated genetic variants in East Asians. Based on data-independent acquisition mass spectrometry technique, we conduct genome-wide association analyses for 304 unique proteins in 2,958 Han Chinese participants. We identify 195 genetic variant-protein associations. Colocalization and Mendelian randomization analyses highlight 60 gene-protein-phenotype associations, 45 of which (75%) have not been prioritized in Europeans previously. Further cross-ancestry analyses uncover key proteins that contributed to the differences in the obesity-induced diabetes and coronary artery disease susceptibility. These findings provide novel druggable proteins as well as a unique resource for the trans-ancestry evaluation of protein-targeted drug discovery.

Description

Keywords

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MC_UU_00006/1)