Related Experiment Video

Updated: May 13, 2026

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

8.5K

Plasma Circulating Proteins and Intracranial Aneurysm Susceptibility: A Proteome-Wide Mendelian Randomization

Xuelun Zou1, Yishu Tang2, Chang Zhou3

  • 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

World Neurosurgery
|April 28, 2025
PubMed

Insights

Biotinidase (BTD) protein levels are associated with reduced intracranial aneurysm (IA) risk, suggesting BTD as a potential biomarker and preventive target for IA. This study used proteome Mendelian randomization to identify key plasma proteins influencing IA.

Area of Science:

  • Genetics
  • Proteomics
  • Cardiovascular Science

Background:

  • Intracranial aneurysms (IAs) are a significant cause of mortality and disability.
  • Effective prevention and treatment strategies for IA are critically needed.

Purpose of the Study:

  • To identify key plasma proteins influencing the risk of intracranial aneurysms (IAs) using a proteome-wide Mendelian randomization approach.
  • To discover potential biomarkers and therapeutic targets for IA prevention and treatment.

Main Methods:

  • Utilized proteome data from 9 studies (2100 plasma proteins) and IA GWAS data from UK Biobank.
  • Employed inverse variance weighting and Wald ratio for primary analysis, with sensitivity analyses including PheWAS and reverse Mendelian randomization.
  • Validated findings using GWAS data from 473,683 European patients and explored therapeutic targets via protein-protein interaction networks and databases.

Main Results:

  • Biotinidase (BTD) and Fc alpha receptor were associated with reduced IA risk, while versican (VCAN) was linked to increased IA risk.
  • Sensitivity analyses confirmed the robustness of these findings against heterogeneity, pleiotropy, and reverse causality.
  • Replication phase confirmed BTD's association with decreased IA risk, but not VCAN or Fc alpha receptor. VCAN emerged as a potential drug target for IA.

Conclusions:

  • Circulating biotinidase (BTD) significantly reduces intracranial aneurysm risk.
  • BTD shows promise as a key biomarker and preventive target for intracranial aneurysms.
Abstract

Keywords:
BiomarkerGenome-wide association analysisIntracranial aneurysmsMendelian randomizationPlasma proteins

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

33.4K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

10.9K

Related Concept Videos

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Increased Intracranial Pressure ll: Pathophysiology01:29

Increased Intracranial Pressure ll: Pathophysiology

Increased intracranial pressure (ICP) refers to a potentially life-threatening rise in pressure inside the skull. This usually happens when there is a major change in the volume of brain tissue, blood, or cerebrospinal fluid (CSF) — the three components inside the skull. According to the Monro-Kellie doctrine, if the volume of one component increases, the volumes of the other components must decrease to maintain normal pressure. If this does not happen, ICP rises.The process often begins with...
Cerebral Edema ll: Pathophysiology01:22

Cerebral Edema ll: Pathophysiology

Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...