Table 1. Genome-wide Association Results for LOAD in the ADGC Stage 1 and Stage 2 datasets.
Association signals represent SNPs with the strongest associations within each locus demonstrating P ≤ 10−6 in the Stage 1 dataset or in/near previously reported genes, excluding the APOE region (Supplementary Table 5).
| SNP | CH:MB | Nearest Gene |
MA | MAF |
# SNPs |
ADGC Discovery (Stage 1) |
ADGC Replication (Stage 2) |
Combined Analysis (Stages 1+2) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ORM (95% CI) |
PM | ORJ (95% CI) |
PJ | ORM (95% CI) |
PM | ORJ (95% CI) |
PJ | ORM (95% CI) |
PM | ORJ (95% CI) |
PJ | ||||||
| rs6701713 | 1:207.8 | CR1* | A | 0.20 | 7 | 1.18 1.11–1.25 |
1.4×10−8 | 1.19 1.12–1.26 |
3.5×10−9 | 1.13 1.04–1.23 |
0.004 | 1.13 1.04–1.24 |
0.004 | 1.16 1.11–1.22 |
4.6×10−10 | 1.17 1.12–1.23 |
5.2×10−11 |
| rs7561528 | 2:127.9 | BIN1* | A | 0.35 | 10 | 1.18 1.13–1.24 |
2.9×10−11 | 1.18 1.12–1.24 |
7.7×10−11 | 1.15 1.07–1.24 |
1.4×10−4 | 1.15 1.07–1.24 |
1.0×10−4 | 1.17 1.13–1.22 |
4.2×10−14 | 1.17 1.12–1.22 |
5.2×10−14 |
| rs9349407 | 6:47.5 | CD2AP | C | 0.27 | 1 | 1.14 1.08–1.21 |
1.2×10−6 | 1.14 1.08–1.20 |
5.3×10−6 | 1.07 0.98–1.17 |
0.118 | 1.08 0.99–1.18 |
0.074 | 1.12 1.07–1.18 |
1.0×10−6 | 1.12 1.07–1.17 |
2.1×10−6 |
| rs11767557 | 7:143.1 | EPHA1‡ | C | 0.19 | 1 | 0.85 0.80–0.90 |
7.3×10−8 | 0.84 0.79–0.89 |
3.1×10−8 | 0.94 0.86–1.03 |
0.169 | 0.93 0.85–1.02 |
0.133 | 0.87 0.83–0.92 |
2.4×10−7 | 0.87 0.83–0.91 |
4.9×10−8 |
| rs1532278 | 8:27.5 | CLU* | T | 0.36 | 2 | 0.90 0.85–0.95 |
5.6×10−5 | 0.89 0.85–0.94 |
2.0×10−5 | 0.87 0.81–0.94 |
2.6×10−4 | 0.87 0.81–0.94 |
2.7×10−4 | 0.89 0.85–0.93 |
8.3×10−8 | 0.89 0.85–0.92 |
1.9×10−8 |
| rs2588969 | 10:63.6 | ARID5B | A | 0.37 | 0 | 0.88 0.84–0.93 |
1.1×10−6 | 0.88 0.84–0.93 |
6.9×10−7 | 1.05 0.97–1.13 |
0.234 | 1.05 0.98–1.13 |
0.189 | 0.93 0.89–0.97 |
0.001 | 0.93 0.89–0.97 |
7.7×10−4 |
| rs4938933 | 11:60.0 | MS4A4A | C | 0.39 | 22 | 0.88 0.84–0.92 |
5.2×10−8 | 0.87 0.83–0.92 |
4.5×10−8 | 0.90 0.84–0.97 |
0.005 | 0.90 0.84–0.97 |
0.004 | 0.88 0.85–0.92 |
1.7×10−9 | 0.88 0.85–0.92 |
1.7×10−9 |
| rs561655 | 11:85.8 | PICALM* | G | 0.34 | 36 | 0.88 0.84–0.92 |
1.2×10−7 | 0.88 0.84–0.93 |
4.6×10−7 | 0.86 0.80–0.93 |
8.4×10−5 | 0.86 0.80–0.92 |
3.7×10−5 | 0.87 0.84–0.91 |
7.0×10−11 | 0.87 0.84–0.91 |
1.0×10−10 |
| rs3752246 | 19:1.1 | ABCA7% | G | 0.19 | 2 | 1.16 1.08–1.24 |
1.0×10−5 | 1.15 1.08–1.23 |
1.9×10−5 | 1.13 1.03–1.24 |
0.012 | 1.13 1.03–1.25 |
0.009 | 1.15 1.09–1.21 |
5.8×10−7 | 1.15 1.09–1.21 |
5.0×10−7 |
| rs3865444 | 19:51.7 | CD33# | A | 0.30 | 1 | 0.88 0.84–0.93 |
8.2×10−7 | 0.88 0.84–0.93 |
1.9×10−6 | 0.91 0.85–0.99 |
0.021 | 0.92 0.85–0.99 |
0.029 | 0.89 0.86–0.93 |
1.1×10−7 | 0.89 0.86–0.93 |
2.0×10−7 |
CH:MB, chromosome:position (in mega base pairs, build 19); MA, minor allele; MAF, minor allele frequency; # SNPs, the number of SNPs for which P ≤ 1 × 10−6 in meta-analysis from the combined analysis in Stage 1+2; ORM, odds ratio in meta-analysis; PM, P-value in meta-analysis; ORJ, odds ratio in joint analysis; PJ, P-value in joint analysis.
Genes with previous case-control genome-wide statistically significant associations: CR13, CLU 1,3, PICALM1, BIN12. Gene with a previous association not meeting genome-wide statistical significance: EPHA12. Family-based association study with reported genome-wide statistical significance: CD3315.
Genes with previously published case-control association signals at P ≤ 5.0 × 10−8 are denoted with *
the case-control locus that did not meet this level of statistical significance is denoted with ‡
the locus previously reported in a family-based association study as genome-wide significant with #
locus identified in Hollingworth et al.12 with genome-wide significant evidence for association with. %