Introduction
Materials and methods
Participants
Genotyping and quality control
Genotype imputation
Diffusion MRI protocol and data processing
Measures of speed of processing
Correlation between FA and measures of speed of processing
GWAS association testing
Meta-analysis
Genetic overlap test between the traits
Multimodal analysis
Voxel-wise analysis
Results
GWAS of WM FA
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 |
GWAS of processing speed
Genetic overlap between two traits: results from GSEA
Gene set | FA gene sets in processing speed | Processing speed gene sets in FA | ||||||
---|---|---|---|---|---|---|---|---|
Size | NES | NOM P value | Validation | Size | NES | NOM P value | Validation | |
Ranked 1–50 | 47 | 0.84 | 0.848 | n.d. | 49 | 1.3 |
0.017
| At 5 % |
Ranked 1–100 | 96 | 0.9 | 0.812 | n.d. | 98 | 1.2 |
0.041
| At 5 % |
Ranked 1–150 | 143 | 0.86 | 0.917 | n.d. | 148 | 1.21 |
0.015
| At 5 % |
Ranked 1–250 | 241 | 0.87 | 0.953 | n.d. | 246 | 1.14 |
0.027
| At 5 % |
Ranked 1–500 | 486 | 1 | 0.511 | n.d. | 485 | 1.14 |
0.004
| At 1 % |
Ranked 1–750 | 735 | 1.01 | 0.441 | n.d. | 725 | 1.09 |
0.03
| At 5 % |
Ranked 1–1000 | 980 | 0.98 | 0.691 | n.d. | 966 | 1.09 |
0.013
| At 5 % |
Ranked 1–2000 | 1965 | 0.97 | 0.828 | n.d. | 1931 | 1.04 | 0.083 | n.d. |