Table 3.
Main Effects (4) | SNP | Subset 1 p-value | Subset 2 p-value | Full Sample p-value | R2 × 100 | CV R2 × 100 | |
F3_rs3917643 | 0.0477 | 0.0270 | 0.0021 | 1.58 | 1.05 | ||
KITLG_rs995029 | 0.0001 | 0.0921 | 0.0001 | 2.33 | 0.96 | ||
CAPN10_rs7571442 | 0.0856 | 0.0318 | 0.0021 | 1.70 | 0.59 | ||
MMP2_rs9928731 | 0.0161 | 0.0383 | 0.0032 | 1.48 | 0.56 | ||
SNP-Covariate Interactions (12) | SNP | Covariate | Subset 1 p-value | Subset 2 p-value | Full Sample p-value | R2 × 100 | CV R2 × 100 |
KITLG_rs1492347 | Log homocysteine | 0.0002 | 0.0640 | 0.0003 | 4.37 | 1.57 | |
ITGB3_rs3851806 | Height | 0.0286 | 0.0101 | 0.0010 | 2.54 | 1.51 | |
TGFB3_rs2284791 | Log C-reactive protein | 0.0073 | 0.0173 | 0.0003 | 2.92 | 1.51 | |
TGFB3_rs2284791 | Physical activity | 0.0885 | 0.0015 | 0.0007 | 2.69 | 1.46 | |
TGFB3_rs2268622 | Log C-reactive protein | 0.0026 | 0.0360 | 0.0003 | 2.86 | 1.42 | |
KITLG_rs995029 | Log homocysteine | 0.0002 | 0.0621 | 0.0003 | 4.42 | 1.40 | |
IL28RA_rs11587500 | LDL particle size | 0.0026 | 0.0014 | 0.0004 | 2.79 | 1.26 | |
ACCN4_rs1872858 | Fibrinogen | 0.0494 | 0.0339 | 0.0010 | 2.59 | 1.24 | |
LTA4H_rs17025079 | Log homocysteine | 0.0006 | 0.0709 | 0.0001 | 3.41 | 1.16 | |
PCSK9_rs10888896 | Log homocysteine | 0.0239 | 0.0567 | 0.0009 | 2.33 | 1.13 | |
IL22RA1_rs3795299 | CHD | 0.0859 | 0.0138 | 0.0009 | 2.41 | 0.70 | |
SERPINE1_rs2227672 | Body mass index | 0.0113 | 0.0219 | 0.0003 | 2.69 | 0.54 | |
SNP-SNP Interactions (20 of 173) | SNP1 | SNP2 | Subset 1 p-value | Subset 2 p-value | Full Sample p-value | R2 × 100 | CV R2 × 100 |
RHAG_rs11759060 | GLS_rs1921913 | 0.0032 | 0.0225 | 8.0 E-06 | 5.49 | 2.61 | |
F8 _rs7053448 | MPO_rs34704261 | 0.0354 | 0.0279 | 0.0001 | 4.10 | 2.58 | |
RHAG_rs11759060 | GLS_rs3771316 | 0.0032 | 0.0225 | 8.0 E-06 | 5.49 | 2.55 | |
MPO_rs34704261 | F8_rs1800291 | 0.0362 | 0.0279 | 0.0001 | 4.10 | 2.44 | |
SLC20A1_rs10758 | IL22RA1_rs12093987 | 0.0439 | 0.0085 | 4.0 E-05 | 5.44 | 2.35 | |
SLC20A1_rs3827758 | IL22RA1_rs12093987 | 0.0315 | 0.0915 | 0.0004 | 3.88 | 2.27 | |
KITLG_rs995029 | TLR4_rs1927911 | 0.0035 | 0.0586 | 5.0 E-05 | 5.58 | 2.27 | |
SLC20A1_rs1053652 | IL22RA1_rs12093987 | 0.0237 | 0.0045 | 5.0 E-05 | 5.07 | 2.22 | |
MPO_rs34704261 | F8_rs4898399 | 0.0433 | 0.0315 | 0.0002 | 4.18 | 2.11 | |
RHAG_rs2518100 | GLS_rs1921913 | 0.0029 | 0.0534 | 0.0001 | 4.50 | 2.11 | |
MMP2_rs243834 | IL28RA_rs4330872 | 0.0136 | 0.0856 | 0.0002 | 4.46 | 2.09 | |
RHAG_rs2518100 | GLS_rs3771316 | 0.0029 | 0.0534 | 0.0001 | 4.50 | 1.95 | |
MPO_rs8077532 | F8_rs1800291 | 0.0417 | 0.0802 | 0.0003 | 3.93 | 1.93 | |
NMUR1_rs10933376 | GPR55_rs2969126 | 0.0945 | 0.0022 | 4.3 E-05 | 5.03 | 1.90 | |
ACCN4_rs3770234 | TNFSF10_rs3136596 | 0.0246 | 0.0007 | 0.0001 | 4.65 | 1.84 | |
PRKAR2B_rs257376 | PKRAR2B_rs3729877 | 0.0085 | 0.0027 | 4.8 E-05 | 3.55 | 1.84 | |
CX3CR1_rs2853712 | F2_rs3136435 | 0.0153 | 0.0480 | 0.0010 | 3.31 | 1.82 | |
KITLG_rs1492347 | TLR4_rs10116253 | 0.0049 | 0.0577 | 0.0001 | 5.44 | 1.81 | |
F8_rs7053448 | MPO_rs8077532 | 0.0417 | 0.0802 | 0.0003 | 3.93 | 1.81 | |
MPO_rs8077532 | F8_rs4898399 | 0.0515 | 0.0822 | 0.0006 | 4.04 | 1.81 |
For all associations, the outcome was leukoaraiosis volume transformed using the natural logarithm and adjusted for age, sex, and total brain volume.
P-value refers to the model p-value (SNP main effects) or the partial F-test p-value of the interaction terms (SNP-Covariate interactions and SNP-SNP interactions).
For SNP-Covariate and SNP-SNP interaction models, CV R2 × 100 refers to the difference in CV R2 × 100 between the full model (including interaction terms) and the reduced model (including main effects only).
ACCN4 amiloride-sensitive cation channel neuronal 4;CAPN10 calpain 10 (cysteine protease); CX3CR1 chemokine, CX3C motif, receptor 1; F2 coagulation factor 2; F3 coagulation factor 3; F8 coagulation factor 8; GLS glutaminase, phosphate activated; GPR55 G protein-coupled receptor 55;IL22RA1 interleukin 22 receptor, alpha-1;IL28RA interleukin 28 receptor; ITGB3 integrin, beta-3; KITLG KIT tyrosine kinase receptor ligand; LTA4H leukotriene A4 hydroxylase; MMP2 matrix metalloproteinase 2 (72 kDa type IV collagenase); MPO myeloperoxidase; NMUR1 neuromedin U receptor 1 (G protein-coupled receptor 66);PCSK9 proprotein convertase, subtilisin/kexin-type, 9;PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta; RHAG rhesus blood group-associated glycoprotein; SERPINE1 plasminogen activator inhibitor 1; SLC20A1 solute carrier family 20 (phosphate transporters), member 1; TGFB3 transforming growth factor, beta 3; TLR4 toll-like receptor 4; TNFSF10 tumor necrosis factor ligand superfamily, member 10