Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics

Autor: Yu-Wen Hsu, Henry Sung-Ching Wong, Wan-Chen Huang, Yi-Hung Yeh, Chwan-Deng Hsiao, Wei-Chiao Chang, Shie-Liang Hsieh
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Biomedical Science, Vol 29, Iss 1, Pp 1-17 (2022)
Druh dokumentu: article
ISSN: 1423-0127
91842298
DOI: 10.1186/s12929-022-00822-1
Popis: 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 (T151→M151) 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.
Databáze: Directory of Open Access Journals
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