Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics.
J Biomed Sci
; 29(1): 43, 2022 Jun 18.
Article
em En
| MEDLINE
| ID: mdl-35717171
ABSTRACT
BACKGROUND:
Human traits, diseases susceptibility, and clinical outcomes vary hugely among individuals. Despite a fundamental understanding of genetic (or environmental) contributions, the detailed mechanisms of how genetic variation impacts molecular or cellular behaviours of a gene, and subsequently leads to such variability remain poorly understood.METHODS:
Here, in addition to phenome-wide correlations, we leveraged multiomics to exploit mechanistic links, from genetic polymorphism to protein structural or functional changes and a cross-omics perturbation landscape of a germline variant.RESULTS:
We identified a missense cis-acting expression quantitative trait locus in CLEC18A (rs75776403) in which the altered residue (T151âM151) disrupts the lipid-binding ability of the protein domain. The altered allele carriage led to a metabolic and proliferative shift, as well as immune deactivation, therefore determines human anthropometrics (body height), kidney, and hematological traits.CONCLUSIONS:
Collectively, we uncovered genetic pleiotropy in human complex traits and diseases via CLEC18A rs75776403-regulated pathways.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Pleiotropia Genética
Limite:
Humans
Idioma:
En
Revista:
J Biomed Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Taiwan