Table 3.
List of novel candidate variants significantly associated with customized genotyping AD chip application set (P value < 0.005).
| Chromosome | SNP | Positionb | Assigned genesc | Functional refGene | Minor/major allele | Our results | Known resultsa | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Groups | MAF in cases | MAF in controls | P valued | OR (CI, 95%) | Non-effect/effect alleles | Beta (SE)e | P value | East Asian frequencyf | European frequency (non-Finnish)f | ||||||
| 1 | rs12063304 | 25071668 | CLIC4 | Upstream | G/A | WGS | 0.041 | 0.086 | 3.07.E−03 | 0.45 (0.26–0.78) | A/G | −0.023 (0.049) | 0.64 | 0.063 | 0.029 |
| cAD chip | 0.032 | 0.055 | 4.98.E−03 | 0.57 (0.38–0.84) | |||||||||||
| Combined | 0.036 | 0.060 | 4.31.E−04 | 0.57 (0.42–0.78) | |||||||||||
| 7 | rs80020083 | 158283748 | PTPRN2 | Intronic | A/G | WGS | 0.038 | 0.077 | 8.67.E−03 | 0.47 (0.27–0.83) | NA | NA | NA | 0.039 | <0.001 |
| cAD chip | 0.035 | 0.060 | 2.60.E−03 | 0.57 (0.39–0.83) | |||||||||||
| Combined | 0.036 | 0.063 | 1.49.E−04 | 0.56 (0.41–0.76) | |||||||||||
| 8 | rs967326 | 18547261 | PSD3 | Intronic | A/G | WGS | 0.334 | 0.219 | 1.08.E−04 | 1.79 (1.32–2.42) | G/A | 0 (0.034) | 1.00 | 0.37 | 0.049 |
| cAD chip | 0.338 | 0.287 | 4.35.E−03 | 1.27 (1.08–1.49) | |||||||||||
| Combined | 0.336 | 0.276 | 4.90.E−05 | 1.33 (1.16–1.53) | |||||||||||
| 10 | rs144835823 | 109002092 | SORCS1,LINC01435 | Intergenic | A/T | WGS | 0.011 | 0.038 | 2.61.E−03 | 0.27 (0.11–0.68) | NA | NA | NA | 0.022 | 0 |
| cAD chip | 0.008 | 0.026 | 8.40.E−04 | 0.32 (0.15–0.65) | |||||||||||
| Combined | 0.009 | 0.028 | 2.42.E−05 | 0.32 (0.19–0.56) | |||||||||||
| 10 | rs78442236 | 109033178 | SORCS1,LINC01435 | Intergenic | A/G | WGS | 0.008 | 0.036 | 1.10.E−03 | 0.21 (0.07–0.59) | NA | NA | NA | 0.020 | 0 |
| cAD chip | 0.004 | 0.022 | 9.57.E−05 | 0.17 (0.06–0.47) | |||||||||||
| Combined | 0.005 | 0.024 | 1.99.E−06 | 0.21 (0.10–0.43) | |||||||||||
| 11 | rs74352072 | 119792009 | LOC102724301,TRIM29 | Intergenic | G/C | WGS | 0.245 | 0.166 | 4.95.E−03 | 1.63 (1.17–2.29) | NA | NA | NA | 0.25 | <0.001 |
| cAD chip | 0.251 | 0.198 | 1.02.E−03 | 1.36 (1.13–1.62) | |||||||||||
| Combined | 0.248 | 0.193 | 3.74.E−05 | 1.39 (1.19–1.61) | |||||||||||
| 15 | rs79919241 | 93434633 | LINC01578 | ncRNA_intronic | T/C | WGS | 0.172 | 0.104 | 6.17.E−03 | 1.80 (1.20–2.70) | C/T | 0.049 (0.039) | 0.21 | 0.066 | 0.043 |
| cAD chip | 0.176 | 0.132 | 1.57.E−03 | 1.40 (1.13–1.73) | |||||||||||
| Combined | 0.174 | 0.127 | 6.11.E−05 | 1.45 (1.21–1.73) | |||||||||||
| 17 | rs201351606 | 1082940 | ABR | Intronic | A/G | WGS | 0.005 | 0.030 | 1.97.E−03 | 0.15 (0.04–0.55) | NA | NA | NA | 0.026 | <0.001 |
| cAD chip | 0.005 | 0.018 | 1.80.E−03 | 0.25 (0.10–0.64) | |||||||||||
| Combined | 0.005 | 0.020 | 3.37.E−05 | 0.23 (0.11–0.48) | |||||||||||
| 17 | rs117665140 | 58280925 | USP32 | Intronic | T/C | WGS | 0.100 | 0.038 | 9.28.E−04 | 2.77 (1.50–5.09) | NA | NA | NA | 0.049 | 0 |
| cAD chip | 0.099 | 0.063 | 8.17.E−04 | 1.62 (1.23–2.13) | |||||||||||
| Combined | 0.099 | 0.059 | 7.73.E−06 | 1.74 (1.37–2.21) | |||||||||||
In the WGS, n = 500; cAD chip n = 1437; combined n = 1937.
AD Alzheimer’s disease, MAF minor allele frequency, OR odds ratio, CI confidence interval, SNP single nucleotide polymorphism, NA not available.
aNon-effect/effect alleles, Beta and P values in the International Genomics of Alzheimer’s Project (IGAP).
bPhysical position based on human reference genome build hg19 (GRCh37).
cThe nearest gene to each SNP is underlined.
dP-values were calculated using Cochran-Armitage trend test.
eOverall estimated effect size and standard error for the effect allele.
fPopulation frequency based on gnomAD database (http://gnomad.broadinstitute.org/).