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Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935862/ https://www.ncbi.nlm.nih.gov/pubmed/36797296 http://dx.doi.org/10.1038/s41467-023-36491-3 |
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author | Xu, Fengzhe Yu, Evan Yi-Wen Cai, Xue Yue, Liang Jing, Li-peng Liang, Xinxiu Fu, Yuanqing Miao, Zelei Yang, Min Shuai, Menglei Gou, Wanglong Xiao, Congmei Xue, Zhangzhi Xie, Yuting Li, Sainan Lu, Sha Shi, Meiqi Wang, Xuhong Hu, Wensheng Langenberg, Claudia Yang, Jian Chen, Yu-ming Guo, Tiannan Zheng, Ju-Sheng |
author_facet | Xu, Fengzhe Yu, Evan Yi-Wen Cai, Xue Yue, Liang Jing, Li-peng Liang, Xinxiu Fu, Yuanqing Miao, Zelei Yang, Min Shuai, Menglei Gou, Wanglong Xiao, Congmei Xue, Zhangzhi Xie, Yuting Li, Sainan Lu, Sha Shi, Meiqi Wang, Xuhong Hu, Wensheng Langenberg, Claudia Yang, Jian Chen, Yu-ming Guo, Tiannan Zheng, Ju-Sheng |
author_sort | Xu, Fengzhe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9935862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99358622023-02-18 Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility Xu, Fengzhe Yu, Evan Yi-Wen Cai, Xue Yue, Liang Jing, Li-peng Liang, Xinxiu Fu, Yuanqing Miao, Zelei Yang, Min Shuai, Menglei Gou, Wanglong Xiao, Congmei Xue, Zhangzhi Xie, Yuting Li, Sainan Lu, Sha Shi, Meiqi Wang, Xuhong Hu, Wensheng Langenberg, Claudia Yang, Jian Chen, Yu-ming Guo, Tiannan Zheng, Ju-Sheng Nat Commun Article 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. Nature Publishing Group UK 2023-02-16 /pmc/articles/PMC9935862/ /pubmed/36797296 http://dx.doi.org/10.1038/s41467-023-36491-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Xu, Fengzhe Yu, Evan Yi-Wen Cai, Xue Yue, Liang Jing, Li-peng Liang, Xinxiu Fu, Yuanqing Miao, Zelei Yang, Min Shuai, Menglei Gou, Wanglong Xiao, Congmei Xue, Zhangzhi Xie, Yuting Li, Sainan Lu, Sha Shi, Meiqi Wang, Xuhong Hu, Wensheng Langenberg, Claudia Yang, Jian Chen, Yu-ming Guo, Tiannan Zheng, Ju-Sheng Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title | Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title_full | Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title_fullStr | Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title_full_unstemmed | Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title_short | Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
title_sort | genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935862/ https://www.ncbi.nlm.nih.gov/pubmed/36797296 http://dx.doi.org/10.1038/s41467-023-36491-3 |
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