Table 2.
Top SNPs demonstrating gene-environment interactions for mental and motor composite scores
| Position | Alleles | Mexico (n = 390) |
Bangladesh (n = 497) |
Meta-analysis | Directiona | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP | Chr | (bp) | Minor/Ref | p | MAF | p | MAF | p | Mapped genes | |
| Mental composite scores | ||||||||||
| rs9642758 | 8 | 35,721,159 | A/G | 0.0004 | 0.076 | 0.0023 | 0.123 | 4.35E-06 | ++ | UNC5D |
| rs2276102 | 11 | 87,013,438 | T/C | 0.0028 | 0.411 | 0.0011 | 0.330 | 1.13E-05 | ++ | TMEM135 |
| rs7952312 | 11 | 99,789,888 | T/G | 0.0031 | 0.365 | 0.0019 | 0.440 | 2.05E-05 | -- | CNTN5 |
| rs7556550 | 1 | 89,928,044 | T/C | 0.0038 | 0.382 | 0.0033 | 0.190 | 4.26E-05 | -- | GBP5/GBP6/LRRC8B/LRRC8C |
| rs619092 | 3 | 173,131,044 | T/C | 0.0018 | 0.248 | 0.0067 | 0.225 | 4.69E-05 | -- | NLGN1 |
| rs10503970 | 8 | 34,866,368 | A/G | 0.0018 | 0.077 | 0.0073 | 0.116 | 4.98E-05 | ++ | UNC5D |
| rs2020402 | 11 | 87,120,819 | T/G | 0.0017 | 0.343 | 0.0090 | 0.403 | 5.98E-05 | -- | LOC101929137/ TMEM135 |
| rs2483678 | 1 | 10,582,047 | T/C | 0.0045 | 0.135 | 0.0043 | 0.308 | 6.31E-05 | -- | PEX14 |
| rs2480786 | 1 | 10,567,658 | A/G | 0.0057 | 0.134 | 0.0037 | 0.299 | 6.94E-05 | ++ | PEX14 |
| rs10270302 | 7 | 150,213,019 | T/C | 0.0021 | 0.071 | 0.0095 | 0.079 | 7.53E-05 | ++ | GIMAP7 |
| rs17035156 | 1 | 10,585,527 | A/C | 0.0050 | 0.133 | 0.0048 | 0.302 | 7.84E-05 | -- | PEX14 |
| rs4811754 | 20 | 55,392,174 | A/C | 0.0031 | 0.423 | 0.0079 | 0.245 | 8.68E-05 | -- | TFAP2C |
| rs1498706 | 12 | 93,996,980 | A/G | 0.0041 | 0.275 | 0.0066 | 0.161 | 9.04E-05 | -- | MRPL42/SOCS2/CRADD |
| rs10493836 | 1 | 90,574,778 | T/C | 0.0053 | 0.083 | 0.0067 | 0.068 | 0.00012 | -- | ZNF326/LRRC8D |
| rs10953862 | 7 | 79,063,644 | A/G | 0.0067 | 0.240 | 0.0060 | 0.292 | 0.00013 | -- | MAGI2 |
| rs1335647 | 1 | 89,832,464 | T/C | 0.0093 | 0.438 | 0.0048 | 0.221 | 0.00014 | ++ | GBP6 |
| rs12120749 | 1 | 52,145,202 | A/G | 0.0098 | 0.253 | 0.0049 | 0.041 | 0.00015 | -- | OSBPL9 |
| rs4734384 | 8 | 99,133,678 | A/C | 0.0075 | 0.260 | 0.0079 | 0.313 | 0.00019 | -- | POP1 |
| rs1349784 | 11 | 99,806,211 | T/G | 0.0067 | 0.383 | 0.0098 | 0.409 | 0.00021 | -- | CNTN5 |
| rs999995 | 10 | 78,735,498 | A/G | 0.0085 | 0.485 | 0.0098 | 0.419 | 0.00026 | ++ | KCNMA1 |
| Motor composite scores | ||||||||||
| rs3817591 | 15 | 33,057,775 | T/C | 5.54E-05 | 0.427 | 0.0031 | 0.490 | 1.16E-06 | -- | FMN1 |
| rs4308495 | 5 | 30,155,798 | T/C | 0.0016 | 0.089 | 0.0019 | 0.121 | 1.15E-05 | ++ | |
| rs28694796 | 7 | 155,403,168 | A/G | 0.0006 | 0.081 | 0.0093 | 0.068 | 2.72E-05 | -- | EN2/RBM33/CNPY1/SHH |
| rs322172 | 17 | 25,659,288 | A/G | 0.0088 | 0.232 | 0.0010 | 0.263 | 2.97E-05 | ++ | MIR4522/WSB1/KSR1 |
| rs10015043 | 4 | 169,485,237 | A/G | 0.0040 | 0.422 | 0.0025 | 0.366 | 3.28E-05 | ++ | PALLD |
| rs13353041 | 1 | 55,773,756 | A/G | 0.0080 | 0.051 | 0.0015 | 0.074 | 3.96E-05 | ++ | USP24/MIR442 |
| rs170602 | 20 | 56,019,162 | T/C | 0.0082 | 0.186 | 0.0016 | 0.210 | 4.19E-05 | ++ | SPO11/RAE1/RBM38/CTCFL/PCK1/ZBP1 |
| rs9945240 | 18 | 44,139,893 | A/G | 0.0067 | 0.062 | 0.0021 | 0.054 | 4.53E-05 | ++ | LOXHD1 |
| rs10022111 | 4 | 169,484,303 | A/G | 0.0018 | 0.459 | 0.0072 | 0.297 | 4.91E-05 | -- | PALLD |
| rs2318817 | 18 | 65,494,366 | A/C | 0.0025 | 0.048 | 0.0064 | 0.119 | 5.57E-05 | ++ | LOC643542 |
| rs2552531 | 2 | 218,698,323 | A/G | 0.0050 | 0.019 | 0.0038 | 0.066 | 6.19E-05 | ++ | TNS1 |
| rs17075573 | 3 | 40,131,246 | T/C | 0.0027 | 0.116 | 0.0086 | 0.082 | 8.38E-05 | -- | MYRIP |
| rs30732 | 5 | 66,151,551 | T/C | 0.0058 | 0.302 | 0.0052 | 0.123 | 9.42E-05 | ++ | MAST4 |
| rs6458566 | 6 | 47,361,788 | A/G | 0.0053 | 0.310 | 0.0056 | 0.467 | 9.50E-05 | ++ | TNFRSF21/CD2AP |
| rs1647292 | 8 | 4,017,692 | T/C | 0.0031 | 0.158 | 0.0091 | 0.177 | 9.83E-05 | -- | CSMD1 |
| rs1324800 | 13 | 48,388,487 | A/G | 0.0033 | 0.041 | 0.0089 | 0.078 | 0.00010 | ++ | SUCLA2 |
| rs16849242 | 3 | 162,188,734 | T/C | 0.0097 | 0.171 | 0.0049 | 0.333 | 0.00014 | ++ | |
| rs17111847 | 1 | 55,749,478 | T/C | 0.0070 | 0.052 | 0.0070 | 0.067 | 0.00015 | -- | USP24/MIR442 |
| rs11600036 | 11 | 81,001,092 | A/G | 0.0062 | 0.135 | 0.0080 | 0.433 | 0.00016 | ++ | |
| rs10122848 | 9 | 25,368,388 | T/G | 0.0071 | 0.073 | 0.0077 | 0.229 | 0.00017 | -- | |
| rs12593647 | 15 | 87,117,255 | A/C | 0.0090 | 0.164 | 0.0090 | 0.262 | 0.00024 | ++ | AGBL1 |
SNP Single-nucleotide polymorphism, MAF minor allele frequency
All models adjusted for child’s gender, child’s age at time of neurodevelopment testing, gestational age, parity, maternal education (binary), environmental tobacco smoke exposure (binary), and first two principal components of population stratification
aEffects of gene-environment interaction on the neurodevelopmental outcomes. “+”: increased risk; “-”: protective effect. The first “+/−” represents the effect observed in Mexico cohort, and the second “+/−” represents the effect observed in Bangladesh cohort