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

Author:

Hsu Yu-Wen,Wong Henry Sung-Ching,Huang Wan-Chen,Yeh Yi-Hung,Hsiao Chwan-Deng,Chang Wei-ChiaoORCID,Hsieh Shie-Liang

Abstract

AbstractBackgroundHuman 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.MethodsHere, 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.ResultsWe identified a missensecis-acting expression quantitative trait locus inCLEC18A(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.ConclusionsCollectively, we uncovered genetic pleiotropy in human complex traits and diseases viaCLEC18Ars75776403-regulated pathways.

Funder

Ministry of Science and Technology, Taiwan

Academia Sinica

VGH, TSGH and AS Joint Research Program

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Biochemistry (medical),Cell Biology,Clinical Biochemistry,Molecular Biology,General Medicine,Endocrinology, Diabetes and Metabolism

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3