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.

Original languageEnglish
Article number43
JournalJournal of Biomedical Science
Issue number1
Publication statusPublished - Dec 2022


  • Body height
  • CLEC18A
  • CLEC18A p.T151M
  • Phosphatidic acid (PA)
  • Phosphatidylserine (PS)
  • rs75776403
  • Thyroid hormone

ASJC Scopus subject areas

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


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