Table 1.
Genome-wide significant and suggestive SNPs from meta-analysis of whole-brain skeleton FA (a), Processing Speed (b), and the multimodality approach (c)
| a | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP | CHR | BP | LD | A1 | A2 | Betula (N = 355) | ||||
| Geno | Rsq | MAF | Beta | P | ||||||
| rs145994492 | 17 | 52423691 | G | A | Imp | 0.89 | 0.032 | –0.0172 | 3.68 × 10−06 | |
| rs7943741 | 11 | 86195270 | G | A | Imp | 1.00 | 0.365 | –0.0048 | 0.00035 | |
| rs6792495 | 3 | 194713051 | C | T | Gen | 1.00 | 0.095 | –0.0093 | 2.98 × 10−05 | |
| rs147652117 | 8 | 106230390 | A | G | Imp | 0.91 | 0.020 | –0.0194 | 4.89 × 10 −05 | |
| rs149603240 | 8 | 106398958 | 0.73 | T | C | Imp | 0.96 | 0.025 | –0.0153 | 0.00029 |
| rs183854424 | 8 | 2778557 | G | T | Imp | 0.80 | 0.076 | –0.0104 | 2.77 × 10−05 | |
| rs10110576 | 8 | 128699454 | A | G | Gen | 1.00 | 0.288 | 0.0042 | 0.00278 | |
|
rs144018030
rs139701334 |
5
5 |
104310291
104517549 |
0.56 |
A
A |
G
C |
Imp
Imp |
0.81
0.66 |
0.014
0.014 |
–0.0146
–0.0146 |
0.00927
0.00927 |
| rs10114823 | 9 | 96510399 | T | C | Imp | 0.99 | 0.028 | –0.0108 | 0.00692 | |
| rs3213603 | 8 | 17188911 | G | A | Imp | 1.00 | 0.203 | –0.0051 | 0.00094 | |
|
rs1232607
rs640336 rs1051421 |
20
20 20 |
10609594
10561369 10620275 |
0.57 0.6 |
T
C T |
C
T C |
Imp
Imp Gen |
1.00
1.00 1.00 |
0.370
0.256 0.283 |
0.0054
0.0067 0.0064 |
8.82 × 10
−05
2.29 × 10−05 3.23 × 10−05 |
| rs2267693 | 7 | 139597043 | G | A | Imp | 0.99 | 0.020 | –0.0171 | 0.0003 | |
| rs115642867 | 3 | 151145469 | G | A | Gen | 1.00 | 0.013 | –0.0217 | 0.00022 | |
| b | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP | CHR | BP | LD | A1 | A2 | Betula (N = 360) | ||||
| Geno | Rsq | MAF | Beta | P | ||||||
| rs6972739 | 7 | 149550942 | T | G | Imp | 0.98 | 0.107 | –3.363 | 2.23 × 10 −06 | |
| rs3823698 | 7 | 149563894 | 0.66 | G | A | Gen | 0.93 | 0.094 | –3.508 | 5.32 × 10−06 |
| rs117443760 | 7 | 149570724 | 0.56 | C | A | Imp | 1.00 | 0.086 | –3.597 | 5.95 × 10−06 |
| rs73168071 | 7 | 149541502 | 0.46 | T | C | Imp | 1.00 | 0.165 | –2.902 | 2.87 × 10−06 |
| rs16930911 | 12 | 26660336 | C | T | Imp | 1.00 | 0.031 | 5.552 | 1.54 × 10−05 | |
| rs1467356 | 12 | 16338172 | G | A | Gen | 0.96 | 0.1859 | –2.884 | 8.65 × 10−07 | |
| rs73785576 | 5 | 126636244 | C | T | Gen | 1.00 | 0.060 | 4.664 | 5.22 × 10−06 | |
| rs61642959 | 4 | 4961319 | T | C | Imp | 0.97 | 0.186 | –2.582 | 5.56 × 10−06 | |
| rs4779527 | 15 | 31736091 | T | C | Gen | 1.00 | 0.110 | –3.705 | 9.61 × 10−07 | |
| rs10776903 | 9 | 137689481 | A | G | Imp | 1.00 | 0.407 | 1.89 | 7.55 × 10−05 | |
| c | |||||||
|---|---|---|---|---|---|---|---|
| SNP | CHR | BP | A1 | A2 | Betula | ||
| Geno | Rsq | MAF | |||||
| rs183854424 | 8 | 2778557 | G | T | Imp | 0.80 | 0.076 |
| rs149603240 | 8 | 106398958 | T | C | Imp | 0.96 | 0.025 |
| rs74887000 | 17 | 41695496 | A | G | Gen | 0.92 | 0.034 |
| a | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| SNP | NCNG (N = 250) | Meta | HGNC Symbol | ||||||
| Geno | Rsq | MAF | Beta | P | Effect | SE | P | ||
| rs145994492 | Imp | 0.54 | 0.014 | –0.0199 | 0.00213 | 0.0179 | 0.0032 | 1.87 × 10−08 | Intergenic |
| rs7943741 | Gen | 1.00 | 0.348 | –0.0062 | 6.03 × 10−05 | 0.0054 | 0.001 | 6.49 × 10−08 | ME3 |
| rs6792495 | Imp | 0.64 | 0.084 | –0.0096 | 0.00089 | 0.0094 | 0.0017 | 6.54 × 10−08 | Intergenic |
|
rs147652117
rs149603240 |
Imp
Imp |
0.77
0.73 |
0.012
0.016 |
–0.0240
–0.0189 |
0.00053
0.00185 |
–0.0209
–0.0165 |
0.0039
0.0034 |
7.44 × 10
−08
1.57 × 10−06 |
ZFPM2
ZFPM2 |
| rs183854424 | Imp | 0.58 | 0.036 | –0.0121 | 0.00197 | 0.0109 | 0.0021 | 1.43 × 10−07 | Closest gene CSMD1 (14 kb downstream) |
| rs10110576 | Imp | 1.00 | 0.41 | 0.0064 | 1.44 × 10−05 | 0.0053 | 0.001 | 1.67 × 10−07 | Intergenic |
|
rs144018030
rs139701334 |
Imp
Imp |
0.83
0.66 |
0.012
0.012 |
–0.0331
–0.0331 |
1.80 × 10
−06
1.80 × 10−06 |
–0.0221
–0.0221 |
0.0043
0.0043 |
2.87 × 10
−07
2.87 × 10−07 |
Intergenic |
| rs10114823 | Imp | 0.97 | 0.03 | –0.0200 | 6.24 × 10−06 | –0.015 | 0.0029 | 2.91 × 10−07 | Intergenic |
| rs3213603 | Imp | 0.97 | 0.204 | –0.0074 | 8.87 × 10−05 | 0.006 | 0.0012 | 3.29 × 10−07 | MTMR7 |
|
rs1232607
rs640336 rs1051421 |
Imp
Imp Gen |
1.00
0.99 1.00 |
0.338
0.21 0.262 |
0.0048
0.0049 0.0045 |
0.00195
0.00754 0.0058 |
0.0051
–0.0059 0.0055 |
0.001
0.0012 0.0011 |
4.54 × 10
−07
5.42 × 10−07 6.51 × 10−07 |
JAG1, SLX4IP
JAG1, SLX4IP JAG1, SLX4IP |
| rs2267693 | Imp | 0.96 | 0.026 | –0.0163 | 0.00069 | 0.0167 | 0.0033 | 5.42 × 10−07 | TBXAS1 |
| rs115642867 | Imp | 0.81 | 0.014 | –0.0206 | 0.00131 | 0.0212 | 0.0043 | 7.57 × 10−07 | IGSF10, MED12L |
| b | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| SNP | NCNG (N = 220) | Meta | HGNC Symbol | ||||||
| Geno | Rsq | MAF | Beta | P | Effect | SE | P | ||
| rs6972739 | Imp | 0.96 | 0.102 | –4.838 | 0.00692 | –3.5613 | 0.6504 | 4.37 × 10 −08 | ZNF862, SSPO, ATP6V0E2 |
| rs3823698 | Gen | 1.00 | 0.096 | –5.386 | 0.00327 | 3.7885 | 0.6999 | 6.21 × 10−08 | ZNF862, SSPO, ATP6V0E2 |
| rs117443760 | Imp | 0.93 | 0.096 | –5.386 | 0.00327 | 3.8785 | 0.7183 | 6.69 × 10−08 | ZNF862, SSPO, ATP6V0E2 |
| rs73168071 | Imp | 0.91 | 0.148 | –3.07 | 0.04028 | –2.9262 | 0.5645 | 2.18 × 10−07 | ZNF862, SSPO, ATP6V0E2 |
| rs16930911 | Imp | 0.96 | 0.042 | 7.117 | 0.003792 | –5.8857 | 1.123 | 1.60 × 10−07 | ITPR2 |
| rs1467356 | Gen | 0.98 | 0.228 | –1.602 | 0.1709 | 2.6327 | 0.5163 | 3.41 × 10−07 | SLC15A5 |
| rs73785576 | Imp | 1.00 | 0.036 | 5.142 | 0.06126 | –4.7212 | 0.9457 | 5.97 × 10−07 | MEGF10 |
| rs61642959 | Imp | 0.98 | 0.178 | –2.34 | 0.06923 | –2.5432 | 0.5131 | 7.17 × 10−07 | Intergenic |
| rs4779527 | Gen | 1.00 | 0.084 | –1.434 | 0.4005 | –3.3415 | 0.6809 | 9.24 × 10−07 | KLF13 |
| rs10776903 | Imp | 1.00 | 0.41 | 2.846 | 0.003372 | 2.076 | 0.4235 | 9.49 × 10−07 | COL5A1 |
| c | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SNP | NCNG | Meta FA | Meta speed task | Fisher–P | HGNC symbol | ||||||
| Geno | Rsq | MAF | Effect | SE | P | Effect | SE | P | |||
| rs183854424 | Imp | 0.58 | 0.036 | 0.0109 | 0.0021 | 1.43 × 10−07 | 1.7805 | 0.8432 | 0.03472 | 1.00 × 10−07 | Closest gene CSMD1 (14 kb downstream) |
| rs149603240 | Imp | 0.74 | 0.016 | –0.0165 | 0.0034 | 1.57 × 10−06 | –3.0633 | 1.4161 | 0.03053 | 8.56 × 10−07 | ZFPM2 |
| rs74887000 | Imp | 0.78 | 0.022 | –0.0098 | 0.003 | 0.00099 | –4.8929 | 1.207 | 5.04E−05 | 8.93 × 10−07 | Intergenic |
A SNP was assigned to a gene if it falls within ±10kbp of the gene based on annotation from ENSEMBL release 66
CHR chromosome, BP base pair position on the GRC human genome assembly 37, LD pair-wise linkage disequilibrium (LD) with the most significant SNP in the close vicinity (bold faced), A1 first allele for the marker, A2 second allele for the marker, Geno shows whether the SNP has directly been genotyped (Geno) or imputed (Imp), Rsq imputation quality estimate r-square value, MAF minor allele (A1) frequency, P P value, effect overall estimated effect size for A1 in the meta-analysis, SE standard error for the overall estimated effect size for A1 in the meta-analysis, P P value, HGNC symbol genes to which the SNPs were assigned