- 作者: Yu-Wen Hsu, Henry Sung-Ching Wong, Wan-Chen Huang, Yi-Hung Yeh, Chwan-Deng Hsiao, Wei-Chiao Chang & Shie-Liang Hsieh
- 作者服務機構: 1.Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan 2.Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 3.Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4.Genomics Research Center, Academia Sinica, Taipei, Taiwan 5.Graduate of Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan 6.Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan 7.Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan 8.Institute of Medical Device and Imaging, National Taiwan University, Taipei, Taiwan 9.Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 10.Integrative Research Center in Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 11.The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
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 identifed 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. - 中文關鍵字:
- 英文關鍵字: CLEC18A, rs75776403, CLEC18A p.T151M, Phosphatidic acid (PA), Phosphatidylserine (PS), Thyroid hormone, Body height