Findings
Background
Subjects and methods
Participants and measurements
Genotyping and statistical analyses
Results and discussion
Autistic-like traitsa | Autistic-like traits domains | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Restricted & repetitive behavior
a
| Social interaction impairment
a
| Language impairment
a
| |||||||||||||||
Gene/SNP | MAF | Genotype | N | All | N | Boys | N | Girls | All | Boys | Girls | All | Boys | Girls | All | Boys | Girls |
CDH9/10
| |||||||||||||||||
rs4307059 | 0.37 (C) | C/C | 1,663 | 0.68 (1.37) | 796 | 0.86 (1.63) | 867 | 0.50 (1.06) | 0.23 (0.57) | 0.31 (0.69) | 0.16 (0.42) | 0.23 (0.57) | 0.29 (0.64) | 0.18 (0.49) | 0.21 (0.52) | 0.27 (0.59) | 0.16 (0.43) |
T/C | 5,564 | 0.73 (1.44) | 2,820 | 0.91 (1.66) | 2,744 | 0.54 (1.14) | 0.23 (0.57) | 0.30 (0.66) | 0.16 (0.45) | 0.25 (0.58) | 0.30 (0.64) | 0.21 (0.50) | 0.24 (0.57) | 0.30 (0.65) | 0.18 (0.46) | ||
T/T | 4,766 | 0.67 (1.36) | 2,391 | 0.85 (1.64) | 2,375 | 0.50 (0.98) | 0.21 (0.55) | 0.28 (0.65) | 0.14 (0.40) | 0.24 (0.58) | 0.29 (0.68) | 0.19 (0.45) | 0.22 (0.54) | 0.27 (0.62) | 0.17 (0.44) | ||
P value | 0.737 | 0.634 | 0.724 | 0.160 | 0.302 | 0.162 | 0.793 | 0.762 | 0.669 | 0.725 | 0.704 | 0.357 | |||||
Effect size (CI 95%)c | 0.007 (-0.033, 0.047) | 0.016 (-0.051, 0.083) | 0.007 (-0.033, 0.048) | 0.011 (-0.004, 0.027) | 0.014 (-0.013, 0.041) | 0.011 (-0.005, 0.028) | -0.002 (-0.018, 0.014) | -0.004 (-0.03, 0.022) | 0.004 (-0.014, 0.022) | 0.003 (-0.019, 0.013) | 0.005 (-0.020, 0.030) | -0.008 (-0.026, 0.009) | |||||
CNTNAP2
| |||||||||||||||||
rs2710102 | 0.48 (G) | A/A | 3,248 | 0.69 (1.37) | 1,618 | 0.87 (1.63) | 1,630 | 0.52 (1.03) | 0.22 (0.57) | 0.29 (0.68) | 0.15 (0.43) | 0.25 (0.57) | 0.30 (0.65) | 0.20 (0.48) | 0.22 (0.53) | 0.27 (0.61) | 0.17 (0.42) |
A/G | 5,976 | 0.70 (1.41) | 2,998 | 0.88 (1.68) | 2,978 | 0.52 (1.04) | 0.22 (0.56) | 0.29 (0.66) | 0.15 (0.42) | 0.24 (0.58) | 0.29 (0.66) | 0.20 (0.47) | 0.23 (0.57) | 0.29 (0.65) | 0.18 (0.46) | ||
G/G | 2,752 | 0.73 (1.45) | 1,382 | 0.90 (1.60) | 1,370 | 0.55 (1.24) | 0.23 (0.58) | 0.31 (0.65) | 0.16 (0.47) | 0.25 (0.58) | 0.29 (0.64) | 0.21 (0.51) | 0.24 (0.56) | 0.30 (0.62) | 0.18 (0.49) | ||
P value | 0.523 | 0.652 | 0.727 | 0.593 | 0.566 | 0.880 | 0.827 | 0.653 | 0.766 | 0.336 | 0.368 | 0.542 | |||||
Effect size (CI 95%)c | 0.013 (-0.026, 0.052) | 0.015 (-0.050, 0.080) | 0.007 (-0.033, 0.048) | 0.004 (-0.011, 0.020) | 0.008 (-0.018, 0.033) | -0.001 (-0.017, 0.015) | -0.002 (-0.018, 0.014) | -0.006 (-0.031, 0.020) | 0.003 (-0.015, 0.020) | 0.008 (-0.008, 0.023) | 0.011 (-0.013, 0.036) | 0.006 (-0.012, 0.023) | |||||
rs7794745 | 0.36 (T) | A/A | 5,004 | 0.72 (1.46) | 2,475 | 0.92 (1.73) | 2,529 | 0.53 (1.10) | 0.24 (0.60) | 0.32 (0.71) | 0.16 (0.44) | 0.25 (0.59) | 0.30 (0.67) | 0.19 (0.49) | 0.24 (0.57) | 0.29 (0.65) | 0.19 (0.47) |
T/A | 5,533 | 0.70 (1.41) | 2,807 | 0.87 (1.63) | 2,726 | 0.53 (1.13) | 0.22 (0.55) | 0.28 (0.63) | 0.15 (0.44) | 0.26 (0.59) | 0.30 (0.66) | 0.21 (0.50) | 0.23 (0.56) | 0.29 (0.64) | 0.17 (0.46) | ||
T/T | 1,564 | 0.67 (1.23) | 779 | 0.82 (1.44) | 785 | 0.51 (0.97) | 0.22 (0.52) | 0.29 (0.59) | 0.15 (0.42) | 0.22 (0.50) | 0.25 (0.58) | 0.20 (0.42) | 0.22 (0.51) | 0.28 (0.59) | 0.16 (0.41) | ||
P value | 0.102 | 0.045b | 0.744 | 0.126 | 0.081 | 0.847 | 0.309 | 0.050b | 0.311 | 0.182 | 0.299 | 0.480 | |||||
Effect size (CI 95%)c | -0.034 (-0.075, 0.007) | -0.069 (-0.136, -0.001) | 0.007 (-0.035, 0.049) | -0.013 (-0.029, 0.004) | -0.024 (-0.051, 0.003) | -0.002 (-0.018, 0.015) | -0.009 (-0.025, 0.008) | -0.026 (-0.053, <0.001) | 0.009 (-0.009, 0.028) | -0.011 (-0.027, 0.005) | -0.014 (-0.039, 0.012) | -0.007 (-0.025, 0.012) | |||||
RELN
| |||||||||||||||||
rs362691 | 0.13 (C) | C/C | 211 | 0.65 (1.34) | 107 | 0.66 (1.11) | 104 | 0.63 (1.54) | 0.22 (0.56) | 0.25 (0.54) | 0.18 (0.58) | 0.25 (0.55) | 0.24 (0.44) | 0.25 (0.65) | 0.18 (0.45) | 0.17 (0.41) | 0.20 (0.49) |
C/G | 2,629 | 0.68 (1.39) | 1,267 | 0.89 (1.69) | 1,362 | 0.49 (1.01) | 0.21 (0.56) | 0.30 (0.68) | 0.14 (0.40) | 0.24 (0.60) | 0.31 (0.71) | 0.18 (0.46) | 0.22 (0.54) | 0.29 (0.61) | 0.16 (0.46) | ||
G/G | 9,139 | 0.71 (1.40) | 4,615 | 0.88 (1.63) | 4,524 | 0.53 (1.09) | 0.22 (0.56) | 0.29 (0.66) | 0.15 (0.43) | 0.25 (0.57) | 0.29 (0.64) | 0.20 (0.48) | 0.23 (0.56) | 0.29 (0.64) | 0.18 (0.45) | ||
P value | 0.338 | 0.629 | 0.659 | 0.350 | 0.739 | 0.612 | 0.944 | 0.835 | 0.980 | 0.282 | 0.306 | 0.659 | |||||
Effect size (CI 95%)c | -0.028 (-0.086, 0.03) | -0.024 (-0.12, 0.072) | -0.013 (-0.073, 0.046) | -0.011 (-0.034, 0.012) | -0.007 (-0.045, 0.032) | -0.006 (-0.03, 0.017) | -0.001 (-0.024, 0.022) | 0.004 (-0.034, 0.042) | <0.001 (-0.026, 0.026) | -0.013 (-0.036, 0.010) | -0.019 (-0.056, 0.018) | -0.006 (-0.032, 0.020) | |||||
SHANK3
| |||||||||||||||||
rs9616915 | 0.49 (T) | C/C | 3,116 | 0.74 (1.53) | 1,589 | 0.96 (1.84) | 1,527 | 0.52 (1.07) | 0.23 (0.60) | 0.32 (0.72) | 0.14 (0.43) | 0.27 (0.62) | 0.33 (0.73) | 0.20 (0.48) | 0.24 (0.58) | 0.31 (0.68) | 0.18 (0.44) |
C/T | 5,839 | 0.68 (1.32) | 2,906 | 0.83 (1.51) | 2,933 | 0.53 (1.08) | 0.22 (0.56) | 0.29 (0.65) | 0.16 (0.44) | 0.24 (0.54) | 0.28 (0.60) | 0.20 (0.47) | 0.22 (0.52) | 0.26 (0.58) | 0.18 (0.45) | ||
T/T | 2,927 | 0.68 (1.38) | 1,461 | 0.88 (1.62) | 1,466 | 0.49 (1.04) | 0.21 (0.53) | 0.29 (0.62) | 0.14 (0.41) | 0.24 (0.56) | 0.28 (0.64) | 0.19 (0.48) | 0.24 (0.57) | 0.31 (0.67) | 0.16 (0.45) | ||
P value | 0.194 | 0.425 | 0.445 | 0.182 | 0.274 | 0.662 | 0.164 | 0.184 | 0.778 | 0.840 | 0.637 | 0.438 | |||||
Effect size (CI 95%)c | -0.026 (-0.064, 0.013) | -0.026 (-0.089, 0.038) | -0.015 (-0.055, 0.024) | -0.010 (-0.026, 0.005) | -0.014 (-0.04, 0.011) | -0.004 (-0.019, 0.012) | -0.011 (-0.027, 0.005) | -0.017 (-0.042, 0.008) | -0.003 (-0.02, 0.015) | -0.002 (-0.017, 0.014) | 0.006 (-0.018, 0.030) | -0.007 (-0.024, 0.010) |
Gene | SNP | Genotype | N (case/control) | P valueb | OR (CI 95%) |
---|---|---|---|---|---|
CDH 9/10
| rs4307059 | C/C | 12/1,651 | 0.835 | 1.087 (0.541-2.184) |
T/C | 37/5,527 | 1.160 (0.714-1.884) | |||
T/T | 36/4,730 | ||||
CNTNAP2
| rs2710102 | A/A | 25/3,223 | 0.800 | 0.806 (0.419-1.551) |
A/G | 44/5,932 | 0.846 (0.468-1.529) | |||
G/G | 17/2,735 | ||||
CNTNAP2
| rs7794745 | A/A | 41/4,963 | 0.125 | 0.351 (0.127-0.972) |
T/A | 40/5,493 | 0.422 (0.152-1.168) | |||
T/T | 5/1,559 | ||||
RELN
| rs362691 | C/C + C/G | 20/2,820 | 0.933 | 1.023 (0.601-1.742) |
G/G | 63/9,076 | ||||
SHANK3
| rs9616915 | C/C | 30/3,086 | 0.094 | 0.764 (0.425-1.373) |
T/C | 31/5,808 | 1.371 (0.769-2.447) | |||
T/T | 21/2,906 |
General NDPa | Impulsivitya | Learning problemsa | Tics and autisma | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene/SNP | MAF | Genotype | N | A ll | N | B oys | N | G irls | A ll | B oys | G irls | A ll | B oys | G irls | A ll | B oys | G irls |
CDH9/10
| |||||||||||||||||
rs4307059 | 0.37(C) | C/C | 1,149 | 0.128 (0.70) | 538 | 0.235 (0.72) | 611 | 0.034 (0.66) | 0.032 (0.53) | 0.034 (0.53) | 0.030 (0.52) | 0.002 (0.59) | 0.017 (0.62) | -0.010 (0.57) | 0.067 (0.51) | 0.144 (0.51) | -0.002 (0.49) |
T/C | 3,923 | 0.172 (0.71) | 1,998 | 0.275 (0.73) | 1,925 | 0.064 (0.68) | 0.028 (0.54) | 0.021 (0.55) | 0.034 (0.53) | 0.051 (0.62) | 0.085 (0.65) | 0.016 (0.58) | 0.069 (0.55) | 0.138 (0.58) | -0.003 (0.50) | ||
T/T | 3,424 | 0.132 (0.69) | 1,711 | 0.244 (0.71) | 1,713 | 0.019 (0.66) | 0.023 (0.54) | 0.038 (0.55) | 0.009 (0.52) | 0.031 (0.62) | 0.066 (0.65) | -0.004 (0.59) | 0.057 (0.50) | 0.105 (0.53) | 0.009 (0.47) | ||
P valueb | 0.962 | 0.661 | 0.811 | 0.554 | 0.571 | 0.959 | 0.401 | 0.474 | 0.702 | 0.734 | 0.702 | 0.695 | |||||
Effect size (CI 95%)c | 0.001 (-0.021, 0.022) | 0.007 (-0.024, 0.037) | -0.004 (-0.034, 0.027) | 0.005 (-0.011, 0.021) | 0.006 (-0.016, 0.029) | 0.001 (-0.024, 0.025) | -0.007 (-0.023, 0.009) | -0.008 (-0.028, 0.013) | -0.005 (-0.033, 0.022) | 0.002 (-0.012, 0.017) | 0.004 (-0.017, 0.025) | 0.004 (-0.018, 0.026) | |||||
CNTNAP2
| |||||||||||||||||
rs2710102 | 0.48(G) | A/A | 2,316 | 0.121 (0.70) | 1,153 | 0.203 (0.72) | 1,163 | 0.040 (0.68) | 0.004 (0.53) | 0.002 (0.54) | 0.007 (0.51) | 0.050 (0.61) | 0.056 (0.62) | 0.043 (0.60) | 0.057 (0.53) | 0.126 (0.56) | -0.012 (0.49) |
A/G | 4,242 | 0.158 (0.70) | 2,126 | 0.274 (0.72) | 2,116 | 0.041 (0.65) | 0.030 (0.54) | 0.037 (0.56) | 0.023 (0.53) | 0.033 (0.63) | 0.075 (0.67) | -0.010 (0.58) | 0.069 (0.52) | 0.125 (0.55) | 0.013 (0.49) | ||
G/G | 1,924 | 0.164 (0.70) | 966 | 0.268 (0.71) | 958 | 0.059 (0.68) | 0.040 (0.54) | 0.036 (0.55) | 0.043 (0.53) | 0.027 (0.60) | 0.063 (0.63) | -0.008 (0.57) | 0.066 (0.53) | 0.130 (0.56) | 0.001 (0.49) | ||
P valueb | 0.501 | 0.135 | 0.634 | 0.344 | 0.315 | 0.767 | 0.450 | 0.692 | 0.167 | 0.768 | 0.856 | 0.746 | |||||
Effect size (CI 95%)c | 0.007 (-0.014, 0.029) | 0.025 (-0.008, 0.057) | -0.006 (-0.032, 0.019) | 0.008 (-0.009, 0.025) | 0.013 (-0.013, 0.039) | 0.003 (-0.018, 0.025) | -0.007 (-0.025, 0.011) | 0.006 (-0.024, 0.037) | -0.015 (-0.037, 0.006) | 0.002 (-0.013, 0.018) | -0.002 (-0.027, 0.022) | 0.002 (-0.008, 0.012) | |||||
rs7794745 | 0.36(T) | A/A | 3,499 | 0.144 (0.70) | 1,714 | 0.251 (0.72) | 1,785 | 0.041 (0.67) | 0.023 (0.53) | 0.028 (0.54) | 0.019 (0.53) | 0.022 (0.61) | 0.048 (0.63) | -0.004 (0.58) | 0.075 (0.53) | 0.140 (0.55) | 0.013 (0.49) |
T/A | 3,947 | 0.156 (0.70) | 2,010 | 0.269 (0.71) | 1,937 | 0.039 (0.67) | 0.028 (0.54) | 0.035 (0.56) | 0.021 (0.53) | 0.046 (0.62) | 0.082 (0.66) | 0.009 (0.58) | 0.058 (0.53) | 0.116 (0.56) | -0.001 (0.49) | ||
T/T | 1,110 | 0.146 (0.70) | 556 | 0.225 (0.73) | 554 | 0.068 (0.65) | 0.031 (0.53) | 0.020 (0.56) | 0.042 (0.51) | 0.042 (0.63) | 0.067 (0.63) | 0.017 (0.62) | 0.050 (0.51) | 0.111 (0.53) | -0.012 (0.48) | ||
P valueb | 0.583 | 0.169 | 0.583 | 0.590 | 0.563 | 0.905 | 0.811 | 0.547 | 0.296 | 0.112 | 0.210 | 0.567 | |||||
Effect size (CI 95%)c | -0.006 (-0.028, 0.016) | -0.023 (-0.055, 0.010) | 0.007 (-0.019, 0.034) | 0.005 (-0.012, 0.021) | 0.007 (-0.017, 0.031) | 0.001 (-0.021, 0.023) | 0.002 (-0.014, 0.018) | -0.008 (-0.032, 0.017) | 0.012 (-0.01, 0.034) | -0.012 (-0.026, 0.003) | -0.015 (-0.038, 0.008) | -0.003 (-0.013, 0.007) | |||||
RELN
| |||||||||||||||||
rs362691 | 0.13(C) | C/C | 156 | 0.097 (0.68) | 80 | 0.149 (0.69) | 76 | 0.043 (0.66) | -0.065 (0.52) | -0.111 (0.45) | -0.017 (0.58) | 0.097 (0.68) | 0.094 (0.56) | 0.100 (0.78) | 0.087 (0.51) | 0.194 (0.53) | -0.025 (0.46) |
C/G | 1,823 | 0.126 (0.69) | 874 | 0.270 (0.69) | 949 | -0.007 (0.65) | 0.019 (0.55) | 0.055 (0.57) | -0.015 (0.53) | 0.025 (0.63) | 0.055 (0.66) | -0.002 (0.60) | 0.063 (0.54) | 0.114 (0.58) | 0.016 (0.49) | ||
G/G | 6,483 | 0.156 (0.70) | 3,270 | 0.253 (0.72) | 3,213 | 0.058 (0.67) | 0.029 (0.53) | 0.023 (0.55) | 0.036 (0.52) | 0.039 (0.61) | 0.071 (0.65) | 0.006 (0.57) | 0.063 (0.52) | 0.128 (0.55) | -0.002 (0.49) | ||
P valueb | 0.545 | 0.879 | 0.288 | 0.444 | 0.856 | 0.115 | 0.957 | 0.802 | 0.521 | 0.632 | 0.715 | 0.646 | |||||
Effect size (95% CI)c | -0.010 (-0.041, 0.022) | 0.003 (-0.04, 0.047) | -0.026 (-0.073, 0.022) | -0.009 (-0.033, 0.014) | 0.003 (-0.029, 0.035) | -0.030 (-0.067, 0.007) | 0.001 (-0.023, 0.024) | -0.004 (-0.033, 0.026) | 0.014 (-0.029, 0.056) | 0.005 (-0.016, 0.026) | 0.006 (-0.025, 0.036) | 0.008 (-0.026, 0.042) | |||||
SHANK3
| |||||||||||||||||
rs9616915 | 0.49(T) | C/C | 2,170 | 0.149 (0.71) | 1,123 | 0.263 (0.73) | 1,047 | 0.028 (0.65) | 0.039 (0.54) | 0.041 (0.56) | 0.037 (0.52) | 0.020 (0.60) | 0.039 (0.62) | 0.001 (0.58) | 0.060 (0.54) | 0.140 (0.55) | -0.025 (0.51) |
C/T | 4,182 | 0.161 (0.70) | 2,044 | 0.266 (0.72) | 2,138 | 0.060 (0.66) | 0.037 (0.54) | 0.053 (0.55) | 0.022 (0.53) | 0.039 (0.61) | 0.075 (0.64) | 0.004 (0.58) | 0.057 (0.52) | 0.096 (0.54) | 0.020 (0.49) | ||
T/T | 2,061 | 0.120 (0.69) | 1,048 | 0.232 (0.70) | 1,013 | 0.005 (0.66) | -0.010 (0.52) | -0.030 (0.54) | 0.011 (0.50) | 0.042 (0.63) | 0.083 (0.68) | -0.001 (0.57) | 0.081 (0.53) | 0.169 (0.58) | -0.009 (0.46) | ||
P valueb | 0.703 | 0.870 | 0.716 | 0.152 | 0.068 | 1.00 | 0.377 | 0.308 | 0.994 | 0.273 | 0.266 | 0.659 | |||||
Effect size (CI 95%)c | 0.004 (-0.017, 0.025) | 0.002 (-0.027, .032) | 0.006 (-0.025, 0.037) | -0.012 (-0.028, 0.004) | -0.020 (-0.042, 0.001) | 0.001 (-0.025, 0.025) | 0.007 (-0.009, 0.023) | 0.011 (-0.01, 0.031) | 0.001 (-0.028, 0.028) | 0.008 (-0.006, 0.022) | 0.012 (-0.009, 0.032) | 0.005 (-0.017, 0.028) |