Table 2.
Single-variant association results in European ancestry individuals excluding the APOE region *
| Chr: Map Position : Effect Allele : Reference Allele | dbSNP ID | Function | Gene Symbol | Stage 1 | Stage 2 Datasets P-value | Stage 1 + 2 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MAC (EA) | MAC (CH) | MAC Total | OR** (95% CI) | Minimum P-value | Best Model | meta | MIRAGE† | NIA-LOAD† | P-value | Direction | ||||
| 6:41129252:C:T | rs75932628 (R47H) | missense | TREM2 | 34 | 0 | 34 | 11.8(5.0–29.1) | 4.56E-12 | M0 | 1.49E-01 | 7.68E-01 | 1.06E-01 | 5.23E-05 | +++ |
| 18:21118536:G:A | rs150334966 | missense | NPC1 | 11 | 0 | 11 | 38.2(6.7–506.4) | 5.78E-09 | M0 | 8.94E-02 | 9.09E-02 | 5.83E-01 | 4.68E-08 | +-- |
| 10:115489177:A:G | rs116437863 | missense | CASP7 | 10 | 0 | 10 | 19.6(5.6–68.2) | 2.44E-10 | M0 | 1.28E-01 | 3.51E-01 | 6.08E-02 | 1.92E-10 | +++ |
| 14:90651236:C:T | rs112153420 | synonymous | KCNK13 | 59 | 2 | 61 | 4.8(2.4–9.3) | 1.55E-07 | M0 | 5.86E-01 | 4.64E-01 | 3.56E-01 | 0.0024 | +-+ |
| 17:46620725:T:A | rs183316427 | missense | HOXB2 | 78 | 5 | 83 | 5.1(2.6–10.2) | 7.63E-08 | M1 | 7.92E-01 | 6.85E-01 | 5.05E-01 | 0.0026 | ++- |
| 11:113846023:C:T | rs62625041 | 5’UTR | HTR3A | 12 | 0 | 12 | 114.9(5.1–24,6) | 1.28E-07 | M1 | 1.23E-01 | 1.33E-01 | 5.23E-01 | 0.012 | +-- |
| 19:14829543:C:T | rs79724046 # | synonymous | ZNF333 | 35 | 26 | 61 | 8.8(3.4–22.0) | 1.28E-07 | M1 | 1.23E-01 | 1.33E-01 | 5.23E-01 | 0.00033 | +++ |
| 3:52552876:C:T | rs372601175 | synonymous | STAB1 | 10 | 0 | 10 | 13.9(3.5–62.7) | 3.58E-07 | M1 | 2.01E-01 | 2.96E-01 | 2.02E-01 | 8.68E-05 | +++ |
| 17:62026823:G:A | rs73992419 # | synonymous | SCN4A | 10 | 19 | 29 | 48.2(9.1–242.1) | 6.30E-14 | M2 | 3.76E-01 | 6.84E-01 | 4.13E-01 | 0.10 | +-- |
| 7:100679240:G:C | rs144027969 | missense | MUC17 | 35 | 0 | 35 | 191.2(11.4–28,0) | 1.63E-09 | M2 | NA | NA | NA | NA | NA |
| 1:109394718:G:T | rs141968711 | missense | AKNAD1 | 11 | 0 | 11 | 22.8(4.6–113.1) | 2.71E-08 | M2 | 1.26E-01 | 2.73E-02 | 2.22E-02 | 0.30 | ++- |
| 1:109394720:C:G | rs747976210 | synonymous | AKNAD1 | 11 | 0 | 11 | 22.8(4.6–113.1) | 2.71E-08 | M2 | 1.26E-01 | 2.73E-02 | 2.22E-02 | 0.30 | ++- |
| 2:97270095:C:T | rs34406082 | missense | KANSL3 | 12 | 7 | 19 | 47.7(6.6–366.3) | 6.40E-08 | M2 | 9.33E-01 | 6.83E-01 | 7.61E-01 | 0.21 | +-+ |
| 15:42565552: CAGA:C | rs550307753 | Inframe deletion | TMEM87A | 11 | 2 | 13 | 36.9(7.4–232.6) | 2.79E-07 | M2 | NA | NA | NA | NA | NA |
| 11:17581152:C:T | rs199968574 | missense | OTOG | 11 | 1 | 12 | 29.3(4.4–161.4) | 4.16E-07 | M2 | 9.90E-02 | 1.51E-01 | 1.07E-01 | 0.78 | +-- |
Table shows variants with p<5.0×10−7, bonferroni significance threshold (i.e., SWS);
OR was based on Firth logistic regression tests;
Family-based ADGC GWAS dataset excluding subjects included in the Stage 1 sample.
variant co-segregated with AD in ≥ 2 CH Stage 2 families;
MAC = minor allele account; EA = European ancestry; CH = Caribbean Hispanic;
OR = Odds Ratio for best model (OR and 95% CI for all three model are provided in Supplementary Table 4) M0 = Model 0: adjustment for PCs and sequencing center;
M1 = Model 1: same adjustments as Model 0 + age and sex;
M2 = Model 2: same adjustments as Model 1 + APOE ɛ4 status and APOE ɛ2 status Study-wide significant results highlighted in bold