Genetic Variants in Intracranial Atherosclerotic Disease: A Systematic Review and Targeted Meta-Analysis Highlighting the RNF213 rs112735431.
Cameron Bass, Patrick Wahlig, Mikayla Hickey et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and targeted meta-analysis examined genetic variants associated with intracranial atherosclerotic disease (ICAD) in human studies identified through September 2025. Fourteen studies included 15 535 individuals, of whom 3638 had ICAD; 35 single-nucleotide variants across 26 genes were reported. In pooled analysis, RNF213 rs112735431 was associated with ICAD (odds ratio, 18.61 [95% CI, 11.84-29.25]). The review also identified variants in ADIPOQ, INSR, and NTNG1, and highlighted lipid metabolism and triglyceride homeostasis pathways.
Key findings
- Fourteen studies included 15 535 individuals, including 3638 with ICAD.
- Pooled analysis associated RNF213 rs112735431 with ICAD (odds ratio, 18.61 [95% CI, 11.84-29.25]).
- Across the studies, 35 variants mapped to 26 genes; other implicated genes included ADIPOQ, INSR, and NTNG1.
- Functional enrichment highlighted lipid metabolism and triglyceride homeostasis pathways.
Why it matters
The findings consolidate evidence that genetic variation may contribute to ICAD susceptibility, with a particularly strong pooled association for RNF213 rs112735431, especially in East Asian populations. The implicated genes and metabolic pathways provide directions for further investigation into disease biology. However, the review does not establish how these variants should be used in clinical assessment or management.
What to keep in mind
The review identifies associations but does not establish causal or functional effects; the authors state that further research is needed to clarify variant function and therapeutic potential.