Association Between Hypoxia-Inducible Factor-1α and Neurological Diseases: A Bidirectional Two-Sample Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Cardiovascular Research

Background:

• Hypoxia-inducible factor 1-alpha (HIF-1α) is implicated in various central nervous system disorders.
• The causal role of plasma HIF-1α in neurological diseases remains unclear.
• This study investigates the potential causal link between plasma HIF-1α and specific neurological conditions.

Purpose of the Study:

• To determine if plasma HIF-1α has a causal effect on cerebrovascular diseases, migraines, and neurodegenerative diseases.
• To utilize Mendelian randomization (MR) to assess causality.
• To explore potential reverse causation from neurological diseases to plasma HIF-1α.

Main Methods:

• Screened single-nucleotide polymorphisms (SNPs) associated with plasma HIF-1α as instrumental variables (IVs).
• Utilized genome-wide association study (GWAS) summary-level data for neurological disorders as outcomes.
• Employed inverse-variance-weighted (IVW) method for primary causal effect analysis and reverse MR for reverse causation.

Main Results:

• Plasma HIF-1α showed a significant genetic association with cardioembolic stroke (CES) (OR = 0.885, p = 0.026).
• Significant associations were also found with migraine (OR = 0.941, p = 0.041) and drug-induced migraine without aura (MOA) (OR = 0.586, p = 0.019).
• No causal link was identified for subarachnoid hemorrhage (SAH), other stroke/migraine subtypes, or neurodegenerative diseases; reverse MR confirmed no reverse causation.

Conclusions:

• Plasma HIF-1α may play a causal role in the risk of CES and migraine, including drug-induced MOA.
• These findings offer novel perspectives for disease prevention and therapeutic strategies.
• The study supports the stability and reliability of the observed associations through sensitivity analyses.