Table 3.
Nonintronic variants with significant differences in allele frequency between affected and control Italian cohorts.
| Gene |
Chr: Position GRCh38
dbSNP |
Ref. Allele |
mRNA
Molecular Consequences |
mRNA Level Affected by SNP eQTL |
CADD (°)
(Ensembl) |
NIG-IT
MAF |
1000G
TSI MAF |
gnomAD 3.1.1 (nfe)
MAF |
p-Value ($)
NIG-IT vs. 1000G TSI |
p-Value ($)
NIG-IT vs. gnomAD 3.1.1 |
| MS-GWAS genes | ||||||||||
| DOCK10 | chr2:224795011:G:A/C rs113265459 |
A | caC/caT p.His1674His |
ns | A:5.937 | 0.0224 | 0 | 0.0165 | 6.87 × 10−7 | 0.1296 |
| NR1D1 | chr17:40100148:G:A rs17616365 |
A | c.-54C > T 5′-UTR |
CASC3, WIPF2 | A:16.11 | 0.0119 | 0.00485 | 0.0283 | 0.00083 | 0.0011 |
| TMEM130 | chr7:98863351:C:T rs199556348 |
T | gcG/gcA p.Ala45Ala | ns | T:1.532 | 0.00046 | 0.00002 | 0.00003 | 0.0013 | 0.0094 |
| Functional partners | ||||||||||
| GRIN2B | chr12:13611840:G:A rs1805482 |
A | agC/agT p.Ser555Ser | ns | A:0.955 | 0.3215 | 0.3786 | 0.3377 | 0.00011 | 0.2569 |
| GRIN2B | chr12:13865843:G:C/T rs7301328 |
C | ccC/ccG p.Pro122Pro | ns | C:7.840 | 0.3646 | 0.4126 | 0.3892 | 0.00131 | 0.0958 |
| PER3 | chr1:7829881:C:T rs2640908 |
T | acC/acT (+) p.Thr978Thr |
VAMP3, UTS2 | T:0.757 | 0.2044 | 0.2379 | 0.1918 | 0.0093 | 0.2884 |
| PER3 | chr1:7830057:T:C rs2640909 |
C | aTg/aCg (+) p.Met1037Thr |
VAMP3 | C:0.161 | 0.2500 | 0.3204 | 0.2872 | 7.27 × 10−7 | 0.0067 |
| PPARGC1A | chr4:23814301:T:C/A rs2970847 |
C | acA/acG p.Thr394Thr |
ns | C:1.605 | 0.1763 | 0.1408 | 0.1923 | 0.00077 | 0.1791 |
| PPARGC1A | chr4:23814039:C:T rs8192678 |
T | Ggt/Agt p.Gly482Ser |
ns | T:16.24 | 0.3572 | 0.4272 | 0.3450 | 3.33 × 10−6 | 0.3964 |
| PPARGC1A | chr4:23813899:C:T/A/G rs3755863 |
T | acG/acA p.Thr528Thr | ns | T:9.102 | 0.4380 | 0.5097 | 0.4054 | 2.42 × 10−6 | 0.0287 |
Genomic coordinates from NCBI Build GRCh38.p13 (hg38) and dbSNP refSNP (rs) identifiers from build 155 are provided. mRNA levels significantly affected by SNPs in vascular and/or brain tissues (reported in GTEx portal as expression quantitative traits, eQTL) are provided. ns, no significant eQTL was found. CASC3, exon junction complex subunit GJD3, involved into spliceosomes at the exon–exon junction; WIPF2, WAS/WASL interacting protein family member 2, involved in the WASP-mediated organization of the actin cytoskeleton. VAMP3, a protein involved in docking/fusion of synaptic vesicles; UTS2, urotensin 2. Minor allele frequency (MAF) from WES of affected subjects collected by the Network for Italian Genomes (NIG-IT); controls from 1000 Genome Tuscany (TSI) and gnomAD 3.1.1 non-Finnish European (nfe) databases are given. ($) Bonferroni’s multiple test correction was set to p < 0.002: in red, SNPs significant after Bonferroni correction; in blue, SNPs at borderline significance after Bonferroni correction; in black, nominally significant variants. (°) Estimated effect on protein function was assessed with the Combined Annotation-Dependent Depletion (CADD) phred-scale scores v1.4 (for convenience, scores above 30 are regarded as “likely deleterious” and scores below as “likely benign”).