Background
Methods
Study subjects
LSR | SAHLSIS | Combined | ||||
---|---|---|---|---|---|---|
Controls (N = 929) | IS cases (N = 2241) | Controls (N = 666) | IS cases (N = 840) | Controls (N = 1595) | IS cases (N = 3081) | |
Age, Median (min, max) | 76 (17, 96) | 76 (18, 102) | 58 (18, 70) | 58 (18, 69) | 66 (17, 96) | 69 (18, 102) |
Male sex, Number (%) | 529 (57) | 1169 (52) | 391 (59) | 550 (66) | 920 (58) | 1719 (56) |
Diabetes mellitus, n | 925 | 2139 | 664 | 840 | 1589 | 2979 |
Number (%) | 69 (8) | 550 (26) | 33 (5) | 153 (18) | 102 (6) | 703 (24) |
Hypertension, n | 925 | 2183 | 665 | 829 | 1590 | 3012 |
Number (%) | 438 (47) | 1479 (68) | 230 (35) | 485 (58) | 668 (42) | 1964 (65) |
Current smoking, n | 927 | 2193 | 666 | 836 | 1593 | 3029 |
Number (%) | 92 (10) | 423 (19) | 131 (20) | 323 (39) | 223 (14) | 746 (25) |
NIHSS at stroke onset, n | -- | 1983 | -- | 581 | -- | 2564 |
0-7, Number (%) | -- | 1482 (75) | -- | 448 (77) | -- | 1930 (75) |
8–15, Number (%) | -- | 338 (17) | -- | 92 (16) | -- | 430 (17) |
16- , Number (%) | -- | 163 (8) | -- | 41 (7) | -- | 204 (7) |
mRS at 3 months, n | -- | 1157 | -- | 565 | -- | 1722 |
0–2, Number (%) | -- | 625 (54) | -- | 435 (77) | -- | 1060 (62) |
3, Number (%) | -- | 196 (17) | -- | 80 (14) | -- | 276 (16) |
4, Number (%) | -- | 111 (10) | -- | 41 (7) | -- | 152 (9) |
5, Number (%) | -- | 92 (8) | -- | 2 (<1) | -- | 94 (5) |
Deceased, Number (%) | -- | 133 (12) | -- | 7 (1) | -- | 140 (8) |
Definition of stroke severity and stroke recovery (outcome)
Phenotypes
Selection of genetic variants and genotyping
Statistical methods
Results
Ischemic stroke risk
SNP* | Allele pair | Control subj. number of genotypes | IS patients number of genotypes | Crude OR (95% CI) | Multiple LR** OR (95% CI) |
---|---|---|---|---|---|
SIGMAR1: | |||||
rs11559048 | CC | 1530 | 2695 | 0.51 (0.21-1.26) | 0.58 (0.91-1.20) |
CT | 8 | 9 |
P = 0.145 |
P = 0.491 | |
TT | 1 | - | |||
rs1800866 | TT | 1128 | 2141 | 1.03 (0.92-1.16) | 1.02 (0.90-1.16) |
TG | 401 | 795 |
P = 0.615 |
P = 0.768 | |
GG | 46 | 88 | |||
rs12001648 | CC | 1393 | 2420 | 0.95 (0.79-1.15) | 0.85 (0.70-1.04) |
CT | 165 | 286 |
P = 0.595 |
P = 0.120 | |
TT | 9 | 8 | |||
rs7036351 | GG | 1130 | 1944 | 1.03 (0.91-1.16) | 1.02 (0.89-1.16) |
GA | 399 | 693 |
P = 0.675 |
P = 0.789 | |
AA | 40 | 77 | |||
rs3808873 | GG | 833 | 1475 | 1.00 (0.89-1.11) | 0.98 (0.88-1.10) |
GA | 491 | 887 |
P = 0.950 |
P = 0.779 | |
AA | 91 | 153 | |||
APOD
:***
| |||||
rs76929107 | CC | 1540 | 2943 | 1.06 (0.74-1.51) | 1.10 (0.75-1.59) |
CT | 44 | 91 |
P = 0.761 |
P = 0.634 | |
TT | 1 | 1 | |||
rs5952 | TT | 1548 | 2710 | 1.90 (0.52-6.92) | 2.23 (0.57-8.75) |
TC | 3 | 10 |
P = 0.329 |
P = 0.251 | |
CC | - | - | |||
rs34697430 | GG | 435 | 769 | 1.00 (0.92-1.09) | 1.01 (0.92-1.11) |
GA | 784 | 1317 |
P = 0.966 |
P = 0.895 | |
AA | 349 | 623 | |||
rs7659 | AA | 803 | 1306 | 1.11 (1.01-1.22) | 1.12 (1.01-1.25) |
AG | 617 | 1177 |
P = 0.038 |
P = 0.029 | |
GG | 130 | 240 | |||
rs823510 | TT | 880 | 1576 | 0.99 (0.89-1.09) | 0.99 (0.89-1.11) |
TG | 590 | 981 |
P = 0.805 |
P = 0.884 | |
GG | 82 | 164 |
Stroke severity and functional outcome
NIHSS score | NIHSS; dichotomous indicator of medium-severe (vs. mild) ischemic stroke onset (NIHSS ≥ 8) | NIHSS; dichotomous indicator of severe (vs. mild-medium) ischemic stroke onset (NIHSS ≥ 16) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Simple logistic regression | Multiple logistic regression | Simple logistic regression | Multiple logistic regression | |||||||
SNP | Estimated Spearman’s Rho |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value |
SIGMAR1: | ||||||||||
rs11559048 | 0.023 | 0.284 | 1.86 (0.44-7.79) | 0.399 | 1.74 (0.40-7.69) | 0.462 | --*) | -- | --*) | -- |
rs1800866 | -0.012 | 0.554 | 1.02 (0.87-1.22) | 0.772 | 0.98 (0.81-1.17) | 0.804 | 0.97 (0.75-1.25) | 0.822 | 0.87 (0.64-1.17) | 0.347 |
rs12001648 | -0.044 | 0.040 | 0.77 (0.56-1.05) | 0.094 | 0.65 (0.46-0.91) | 0.012 | 1.01 (0.66-1.56) | 0.967 | 0.75 (0.48-1.27) | 0.283 |
rs7036351 | 0.000 | 0.984 | 1.04 (0.87-1.25) | 0.670 | 0.99 (0.81-1.21) | 0.922 | 0.94 (0.71-1.25) | 0.664 | 0.84 (0.61-1.16) | 0.290 |
rs3808873 | 0.011 | 0.627 | 1.04 (0.88-1.23) | 0.619 | 1.07 (0.90-1.27) | 0.457 | 0.79 (0.61-1.03) | 0.084 | 0.77 (0.57-1.03) | 0.079 |
APOD:
| ||||||||||
rs76929107 | 0.004 | 0.826 | 0.85 (0.50-1.46) | 0.555 | 0.74 (0.40-1.36) | 0.327 | 0.97 (0.45-2.12) | 0.948 | 1.17 (0.50-2.73) | 0.722 |
rs5952 | 0.022 | 0.309 | 1.54 (0.38-6.18) | 0.542 | 1.40 (0.34-5.79) | 0.641 | --*) | -- | --*) | -- |
rs34697430 | 0.011 | 0.599 | 1.07 (0.93-1.23) | 0.334 | 1.08 (0.94-1.25) | 0.280 | 1.16 (0.95-1.42) | 0.154 | 1.20 (0.96-1.50) | 0.116 |
rs7659 | -0.048 | 0.023 | 0.89 (0.77-1.04) | 0.141 | 0.85 (0.72-1.00) | 0.044 | 0.84 (0.66-1.06) | 0.135 | 0.70 (0.54-0.92) | 0.009 |
rs823510 | 0.013 | 0.538 | 1.03 (0.88-1.21) | 0.680 | 1.00 (0.85-1.19) | 0.965 | 1.06 (0.83-1.34) | 0.658 | 0.96 (0.73-1.25) | 0.736 |
NIHSS score | NIHSS; dichotomous indicator of medium-severe (vs. mild) ischemic stroke onset (NIHSS ≥ 8) | NIHSS; dichotomous indicator of severe (vs. mild-medium) ischemic stroke onset (NIHSS ≥ 16) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Subgroup | Estimated Spearman’s Rho |
P-value | Simple logistic regression | Multiple logistic regression | Simple logistic regression | Multiple logistic regression | ||||
OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | |||
Total | -0.048 | 0.023 | 0.89 (0.77-1.04) | 0.141 | 0.85 (0.72-1.00) | 0.044 | 0.84 (0.66-1.06) | 0.135 | 0.70 (0.54-0.92) | 0.009 |
(N = 2221) | 1676 controls | 1618 controls | 2023 controls | 1947 controls | ||||||
545 cases | 495 cases | 198 cases | 166 cases | |||||||
Males | -0.055 | 0.053 | 0.89 (0.72-1.11) | 0.293 | 0.85 (0.68-1.06) | 0.143 | 0.82 (0.58-1.17) | 0.273 | 0.75 (0.52-1.10) | 0.144 |
(N = 1232) | 971 controls | 939 controls | 1146 controls | 1105 controls | ||||||
261 cases | 243 cases | 86 cases | 77 cases | |||||||
Females | -0.040 | 0.209 | 0.90 (0.73-1.11) | 0.311 | 0.85 (0.68-1.07) | 0.168 | 0.85 (0.62-1.16) | 0.311 | 0.66 (0.46-0.96) | 0.028 |
(N = 989) | 705 controls | 679 controls | 877 controls | 842 controls | ||||||
284 cases | 252 cases | 112 cases | 89 cases | |||||||
LSR | -0.054 | 0.026 | 0.87 (0.73-1.03) | 0.113 | 0.81 (0.67-0.98) | 0.026 | 0.79 (0.61-1.03) | 0.081 | 0.65 (0.48-0.88) | 0.005 |
(N = 1683) | 1263 controls | 1204 controls | 1523 controls | 1450 controls | ||||||
420 cases | 377 cases | 160 cases | 133 cases | |||||||
SAHLSIS | -0.032 | 0.454 | 0.97 (0.71-1.33) | 0.858 | 0.94 (0.68-1.30) | 0.702 | 1.03 (0.62-1.73) | 0.902 | 0.86 (0.48-1.53) | 0.605 |
(N = 538) | 413 controls | 412 controls | 500 controls | 497 controls | ||||||
125 cases | 118 cases | 38 cases | 33 cases | |||||||
Age < 70 | -0.066 | 0.029 | 0.89 (0.70-1.13) | 0.333 | 0.85 (0.67-1.09) | 0.201 | 0.98 (0.66-1.47) | 0.940 | 0.81 (0.51-1.27) | 0.348 |
(N = 1084) | 868 controls | 853 controls | 1021 controls | 1001 controls | ||||||
216 cases | 202 cases | 63 cases | 54 cases | |||||||
Age ≥ 70 | -0.042 | 0.156 | 0.88 (0.72-1.08) | 0.215 | 0.82 (0.66-1.02) | 0.080 | 0.76 (0.57-1.01) | 0.060 | 0.63 (0.45-0.88) | 0.006 |
(N = 1137) | 808 controls | 750 controls | 1002 controls | 946 controls | ||||||
329 cases | 266 cases | 135 cases | 112 cases | |||||||
LVD | -0.008 | 0.918 | 1.14 (0.70-1.87) | 0.597 | 0.97 (0.57-1.66) | 0.924 | 1.20 (0.54-2.67) | 0.651 | 0.53 (0.17-1.65) | 0.272 |
(N = 185) | 133 controls | 128 controls | 170 controls | 163 controls | ||||||
52 cases | 45 cases | 15 cases | 10 cases | |||||||
SVD | -0.019 | 0.667 | 0.77 (0.46-1.30) | 0.329 | 0.81 (0.47-1.38) | 0.432 | N/A | N/A | ||
(N = 500) | 461 controls | 452 controls | ||||||||
39 cases | 38 cases | |||||||||
CE | -0.076 | 0.065 | 0.89 (0.70-1.15) | 0.367 | 0.78 (0.59-1.03) | 0.081 | 0.72 (0.52-1.00) | 0.051 | 0.59 (0.40-0.85) | 0.005 |
(N = 595) | 364 controls | 338 controls | 484 controls | 448 controls | ||||||
231 cases | 204 cases | 111 cases | 94 cases |
Deceased patientsare notincluded in mRS: | Deceased patientsareincluded in mRS: | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Ordinal score: | Dichotomous indicator for dependence of support: | Ordinal score: | Dichotomous indicator for dependence of support: | |||||||||
SNP | Estimated Spearman’s Rho |
P-value | Simple logistic regression | Multiple logistic regression | Estimated Spearman’s Rho |
P-value | Simple logistic regression | Multiple logistic regression | ||||
OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | OR (95% CI) |
P-value | |||||
SIGMAR1: | ||||||||||||
rs11559048 | 0.045 | 0.081 | 3.35 (0.80-14.1) | 0.099 | 2.75 (0.49-15.3) | 0.249 | 0.026 | 0.286 | 2.64 (0.63-11.1) | 0.185 | 2.29 (0.38-13.7) | 0.364 |
rs1800866 | 0.011 | 0.655 | 1.13 (0.93-1.37) | 0.231 | 1.10 (0.88-1.36) | 0.404 | 0.004 | 0.872 | 1.08 (0.90-1.30) | 0.402 | 1.06 (0.85-1.31) | 0.612 |
rs12001648 | -0.012 | 0.631 | 0.94 (0.67-1.32) | 0.712 | 0.77 (0.53-1.11) | 0.165 | -0.001 | 0.963 | 0.98 (0.72-1.34) | 0.892 | 0.75 (0.53-1.07) | 0.115 |
rs7036351 | 0.006 | 0.817 | 1.10 (0.89-1.33) | 0.390 | 1.03 (0.83-1.29) | 0.781 | -0.007 | 0.772 | 1.04 (0.86-1.25) | 0.722 | 0.97 (0.79-1.21) | 0.810 |
rs3808873 | 0.021 | 0.436 | 1.08 (0.90-1.29) | 0.392 | 1.11 (0.91-1.35) | 0.290 | 0.012 | 0.636 | 1.05 (0.89-1.24) | 0.598 | 1.07 (0.89-1.30) | 0.457 |
APOD: | ||||||||||||
rs76929107 | 0.002 | 0.947 | 0.98 (0.54-1.78) | 0.943 | 0.95 (0.49-1.82) | 0.868 | -0.013 | 0.582 | 0.87 (0.49-1.54) | 0.623 | 0.92 (0.48-1.73) | 0.790 |
rs5952 | 0.016 | 0.520 | 1.98 (0.28-14.1) | 0.494 | 2.90 (0.32-26.7) | 0.346 | 0.025 | 0.306 | 2.35 (0.39-14.1) | 0.350 | 3.09 (0.35-27.5) | 0.312 |
rs34697430 | -0.019 | 0.460 | 0.91 (0.78-1.06) | 0.221 | 0.91 (0.77-1.07) | 0.243 | 0.002 | 0.946 | 0.96 (0.83-1.10) | 0.514 | 0.92 (0.79-1.08) | 0.295 |
rs7659 | 0.002 | 0.929 | 1.03 (0.88-1.22) | 0.684 | 0.98 (0.82-1.17) | 0.832 | -0.005 | 0.846 | 1.02 (0.87-1.18) | 0.842 | 0.96 (0.81-1.14) | 0.665 |
rs823510 | 0.012 | 0.653 | 1.01 (0.85-1.21) | 0.882 | 1.02 (0.84-1.23) | 0.871 | -0.008 | 0.742 | 0.97 (0.82-1.14) | 0.696 | 0.97 (0.81-1.17) | 0.764 |