A rare cerebral vasculopathy that narrows the brain's major arteries and can cause stroke in children or young adults — a 2018 GWAS found 10 new risk loci, and one surprising signal tied to homocysteine metabolism rather than the disease's usual dominant gene.
Moyamoya disease (MMD) is a rare cerebral vasculopathy — a progressive narrowing of the internal carotid arteries at the base of the brain — that often leads to stroke in children or young adults. Familial cases are well recognized, but the full genetic basis had remained poorly understood.
Duan et al. 2018 conducted a two-stage genome-wide association study of 1,492 people with MMD and 5,084 controls, finding 10 new genome-wide-significant risk loci and confirming a previously known locus at 17q25 — home to RNF213, the gene most consistently implicated in moyamoya disease across populations. Together, all associated loci explained an estimated 14.76% of disease risk variance, out of 39.02% explained by all genome-wide genotyped SNPs combined — a substantial share, though most of the heritable risk remains unaccounted for by any confirmed variant.
Two of this page's variants, rs9907978 and rs10782008, are both in RNF213 itself, with odds ratios of 1.59 and 2.0 respectively — distinct from rs9916351, the specific RNF213 SNP the paper highlights as showing a notably stronger effect in early-onset than late-onset disease. Two more, rs9614159 (HORMAD2, OR 1.4) and rs74388387 (MAGI2, OR 1.61), are among the newly identified loci outside the RNF213 region.
The fifth variant, rs117353193, in TCN2, is not itself a moyamoya risk locus in the usual sense — it was found associated with high serum homocysteine specifically among people who already have moyamoya disease (odds ratio 1.43), alongside a second homocysteine-pathway variant in MTHFR not held on this site. Both genes regulate homocysteine metabolism, and the paper's tissue-enrichment analysis separately found MMD-associated genes highly expressed in the immune system — together pointing toward metabolic and immune pathways as areas worth investigating for treatment, rather than a single mechanism.
Moyamoya disease is diagnosed by brain imaging showing the characteristic arterial narrowing and its "puff of smoke" collateral vessels, not by genotype. None of the 5 variants on this page are used by any guideline to diagnose MMD or predict who will develop it.
The homocysteine finding in particular is a population-level association within people already diagnosed with MMD, not a screening test or a treatment recommendation — the paper's own framing is that homocysteine metabolism and immune pathways are worth investigating further, not that they are established treatment targets today.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Moyamoya Disease comes down to these specific, well-studied positions — not a diagnosis.
Databases, guidelines and references
Moyamoya disease (MMD) is a rare cerebral vasculopathy — a progressive narrowing of the brain's major arteries — that often causes stroke in children or young adults.
Studying 1,492 people with MMD and 5,084 controls, it found 10 new genome-wide-significant risk loci and confirmed the previously known RNF213 locus, together explaining an estimated 14.76% of disease risk variance.
Yes — RNF213, at 17q25, is the most consistently confirmed moyamoya susceptibility gene across populations. Two of this page's variants are in RNF213 itself.
One variant on this page, in TCN2, was associated with high serum homocysteine specifically among people already diagnosed with moyamoya disease — a metabolic pathway the study flags as worth investigating further, not a diagnostic marker or treatment target today.
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