Japanese variant	Japanese wild-type	Polish	P value	Odds ratio, 95% CI
Affected hemispheres, number	120	53	57	Japanese variant vs Polish	Japanese variant vs Japanese wild-type	Japanese variant vs Polish	Japanese variant vs Japanese wild-type
Suzuki angiographical stage, number
Stage 1	12	8	2	0.26	0.24	3.1 (0.72-14)	0.63 (0.25-1.6)
Stage 2	23	7	9	1.3 (0.54-3.1)	1.6 (0.66-4.0)
Stage 3	28	12	15	0.85 (0.41-1.8)	1.0 (0.47-2.3)
Stage 4	36	12	20	0.79 (0.40-1.6)	1.5 (0.69-3.1)
Stage 5	21	12	9	1.1 (0.48-2.8)	0.72 (0.33-1.7)
Stage 6	0	2	2	0 (0-1.0)	0 (0-0.95)
Transdural collateral, number, percentage of total for each stage (%)
Total	53 (44%)	18 (34%)	34 (60%)
Stage 1	0 (0%)	0 (0%)	0 (0%)	0.68	0.0026**	N.A.	N.A.
Stage 2	3 (13%)	2 (29%)	2 (22%)	0.53 (0.26-1.1)	0.37 (0.18-0.74)**
Stage 3	12 (43%)	3 (25%)	7 (47%)	0.85 (0.48-1.5)	2.3 (1.2-4.1)*
Stage 4	21 (58%)	4 (33%)	15 (75%)	0.46 (0.26-0.84)*	2.8 (1.6-5.0)***
Stage 5&6	17 (81%)	9 (64%)	10 (91%)	0.42 (0.17-1.0)	2.4 (1.3-4.5)*
Grade2 PA collateral, number, percentage of total for each stage (%)
Total	43 (36%)	11 (21%)	7 (12%)
Stage 1	0 (0%)	0 (0%)	0 (0%)	<0.0001****	<0.0001****	N.A.	N.A.
Stage 2	0 (0%)	3 (43%)	0 (0%)	N.A.	0 (0-0.046)**
Stage 3	12 (43%)	4 (33%)	3 (20%)	3.0 (1.6-5.5)***	1.5 (0.87-2.7)
Stage 4	19 (53%)	4 (33%)	4 (20%)	4.5 (2.4-8.2)****	2.3 (1.3-4.1)**
Stage 5&6	12 (57%)	0 (0%)	0 (0%)	Infinity (38-infinity)****	Infinity (38-infinity)****
PCA leptomeningeal collateral, number, percentage of total for each stage (%)
Total	96 (80%)	42 (79%)	50 (88%)
Stage 1	2 (17%)	0 (0%)	0 (0%)	0.98	0.61	Infinity (0.066-infinity)	Infinity (0.31-infinity)
Stage 2	15 (65%)	7 (100%)	9 (100%)	0 (0-0.81)	0 (0-1.1)
Stage 3	23 (82%)	9 (75%)	12 (80%)	1.2 (0.27-5.9)	1.5 (0.35-8.5)
Stage 4	35 (97%)	12 (100%)	19 (95%)	1.8 (0.092-36)	0 (0-27)
Stage 5&6	21 (100%)	14 (100%)	10 (91%)	Infinity (0.21-infinity)	N.A.

Supplementary Table

Comparison of angiographical stages and natural collateral formation between Japanese patients carrying the RNF213 p.R4810K variant and Polish Caucasian patients, as well as between Japanese patients with the variant and those with the wild-type genotype. Note that all Polish Caucasian patients carried the wild-type RNF213 p.R4810K genotype, whereas all Japanese patients with the variant were heterozygous. Because no Japanese patients with the variant genotype were classified as Suzuki stage 6, stages 5 and 6 were combined into a single category for comparisons of natural collateral formation in these supplementary analyses.

PA: periventricular anastomosis, PCA: posterior cerebral artery, N.A.: not applicable for odds ratio calculation

**: P<0.01, ****: P<0.0001

Supplementary FIG. 1. Subgroup Comparisons in Japanese cohort for Suzuki angiographical stage (A), natural transdural collateral formation (B), and prominent grade 2 periventricular anastomosis (PA) collateral formation (C) between patients with and without RNF213 p.R4810K variant. ns: not significant,

**: P<0.01. ****: P<0.0001

Supplementary FIG. 2. Subgroup Comparisons for Suzuki angiographical stage (A), natural transdural collateral formation (B), and prominent grade 2 periventricular anastomosis (PA) collateral formation (C) between Polish patients and Japanese patients with RNF213 p.R4810K variant. ns: not significant,

****: P<0.0001

Supplementary FIG. 3. Subgroup Comparisons for posterior cerebral artery (PCA) derived leptomeningeal collateral formation among Japanese entire cohort, Polish Caucasian patients, Japanese patients with RNF213 p.R4810K variant, and those with RNF213 p.R4810K wild-type. ns: not significant