Table 3.
Gene-based association of rare and low frequency protein-modifying variants in NOTCH3, COL4A1, and COL4A2 genes with extreme cerebral SVD
| Genea (Transcript) | 3C-Dijon (Discovery, n = 512) | ARIC, CHS, FHS and RS1 (Replication, n = 956) | Combined (n = 1467) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Variants, n | Cumulative MAF | P (SKAT-O)* | P (SKAT-O) additional adjusted for HT status | Variants, n | Cumulative MAF | P (SKAT-O) | P (SKAT-O) additional adjusted of HT status | P (SKAT-O) | |
| NOTCH3 (ENST00000263388) | 31 | 0.10 | 1.61 × 10−2 | 1.58 × 10−2 | 36 | 0.11 | 3.99 × 10−2 | 4.60 × 10−2 | 5.31 × 10−3 |
| COL4A2 (ENST00000360467) | 29 | 0.09 | 0.23 | 0.19 | NA | NA | NA | NA | NA |
| COL4A1 (ENST00000375820) | 13 | 0.02 | 0.40 | 0.48 | NA | NA | NA | NA | NA |
aSorted by SKAT-O P-value in discovery cohort.
*Significance threshold for discovery is SKAT-O P-value < 1.67 × 10−2 correcting for three tested genes.
ARIC = Atherosclerosis Risk In Communities; CHS = Cardiovascular Health Study; FHS = Framingham Heart Study; HT = hypertension; MAF = minor allele frequency; RS1 = Rotterdam Study 1.