Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00571761" target="_blank" >RIV/68378050:_____/23:00571761 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/hmg/article/32/8/1266/6812863?login=true" target="_blank" >https://academic.oup.com/hmg/article/32/8/1266/6812863?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/hmg/ddac275" target="_blank" >10.1093/hmg/ddac275</a>
Alternative languages
Result language
angličtina
Original language name
Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing
Original language description
Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356, 22.5x WGS) and Pomak (n = 1537, 18.4x WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populations but have drifted up in the frequency in the discovery cohorts here. We identify proteins causally associated with cardiometabolic traits, including Mep1b for high-density lipoprotein (HDL) levels, and describe a knock-out (KO) Mep1b mouse model. Our findings furnish insights into the genetic architecture of the serum proteome, identify new protein-disease relationships and demonstrate the importance of isolated populations in pQTL analysis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Molecular Genetics
ISSN
0964-6906
e-ISSN
1460-2083
Volume of the periodical
32
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
1266-1275
UT code for WoS article
000908330700001
EID of the result in the Scopus database
2-s2.0-85152172014