Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics
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 su...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12929-022-00822-1 |
| _version_ | 1811343456715407360 |
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| author | Yu-Wen Hsu Henry Sung-Ching Wong Wan-Chen Huang Yi-Hung Yeh Chwan-Deng Hsiao Wei-Chiao Chang Shie-Liang Hsieh |
| author_facet | Yu-Wen Hsu Henry Sung-Ching Wong Wan-Chen Huang Yi-Hung Yeh Chwan-Deng Hsiao Wei-Chiao Chang Shie-Liang Hsieh |
| author_sort | Yu-Wen Hsu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:29:39Z |
| format | Article |
| id | doaj.art-096816c0f91842298f922824b1f59ab8 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-04-13T19:29:39Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-096816c0f91842298f922824b1f59ab82022-12-22T02:33:13ZengBMCJournal of Biomedical Science1423-01272022-06-0129111710.1186/s12929-022-00822-1Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomicsYu-Wen Hsu0Henry Sung-Ching Wong1Wan-Chen Huang2Yi-Hung Yeh3Chwan-Deng Hsiao4Wei-Chiao Chang5Shie-Liang Hsieh6The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia SinicaDepartment of Clinical Pharmacy, School of Pharmacy, Taipei Medical UniversityInstitute of Cellular and Organismic Biology, Academia SinicaInstitute of Molecular Biology, Academia SinicaInstitute of Molecular Biology, Academia SinicaDepartment of Clinical Pharmacy, School of Pharmacy, Taipei Medical UniversityGenomics Research Center, Academia SinicaAbstract 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.https://doi.org/10.1186/s12929-022-00822-1CLEC18Ars75776403CLEC18A p.T151MPhosphatidic acid (PA)Phosphatidylserine (PS)Thyroid hormone |
| spellingShingle | Yu-Wen Hsu Henry Sung-Ching Wong Wan-Chen Huang Yi-Hung Yeh Chwan-Deng Hsiao Wei-Chiao Chang Shie-Liang Hsieh Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics Journal of Biomedical Science CLEC18A rs75776403 CLEC18A p.T151M Phosphatidic acid (PA) Phosphatidylserine (PS) Thyroid hormone |
| title | Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics |
| title_full | Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics |
| title_fullStr | Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics |
| title_full_unstemmed | Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics |
| title_short | Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics |
| title_sort | human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a clec18a p t151m driven multiomics |
| topic | CLEC18A rs75776403 CLEC18A p.T151M Phosphatidic acid (PA) Phosphatidylserine (PS) Thyroid hormone |
| url | https://doi.org/10.1186/s12929-022-00822-1 |
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