TABLE 2.
MAPT‐haplotype specific associations
| Unstratified d | H2 non‐carriers d | H2 carriers d | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SNPa | CHR b | Position b | Closest gene c | Major/Ref allele b | Minor/Alt allele b | Nj e | ORJ (95% CI) e | Pj e | Nm f | ORm f | Pm f | Nj e | ORJ (95% CI) e | Pj e | Nm f | ORm f | Pm f | Nj e | ORJ (95% CI) e | Pj e | Nm f | ORm f | Pm f | Epistatis P g |
| Discordant loci with P ≤ 1E‐5 in the H2 non‐carriers a.1 | ||||||||||||||||||||||||
| rs4555724 | 4 | 141658697 | TBC1D9 | T | C | 18797 | 0.91 (0.87‐0.95) | 3.64E‐05 | 21 | 0.92 | 3.19E‐03 | 11454 | 0.87 (0.82‐0.92) | 8.64E‐07 | 21 | 0.87 | 1.11E‐05 | 7343 | 0.98 (0.92‐1.06) | 6.60E‐01 | 21 | 0.99 | 6.95E‐01 | 6.78E‐03 |
| rs28705797 | 4 | 173902942 | GALNTL6 | A | C | 18759 | 1.13 (1.06‐1.2) | 1.12E‐04 | 21 | 1.13 | 1.97E‐04 | 11424 | 1.21 (1.12‐1.32) | 2.10E‐06 | 21 | 1.21 | 4.73E‐06 | 7335 | 1.02 (0.92‐1.13) | 6.96E‐01 | 21 | 1.00 | 9.37E‐01 | 7.96E‐03 |
| rs1685555 | 8 | 89483894 | MMP16;LOC101929709 | A | G | 18637 | 0.79 (0.69‐0.9) | 5.13E‐04 | 21 | 0.79 | 1.08E‐02 | 11371 | 0.68 (0.57‐0.81) | 9.49E‐06 | 20 | 0.67 | 3.08E‐04 | 7266 | 1 (0.81‐1.24) | 9.79E‐01 | 20 | 1.02 | 8.78E‐01 | 4.98E‐03 |
| rs4354897 | 15 | 84644971 | ADAMTSL3 | T | C | 18707 | 0.91 (0.87‐0.96) | 2.90E‐04 | 21 | 0.91 | 5.72E‐03 | 11397 | 0.84 (0.79‐0.9) | 2.04E‐07 | 21 | 0.84 | 1.22E‐06 | 7310 | 1.03 (0.95‐1.12) | 4.87E‐01 | 21 | 1.02 | 7.13E‐01 | 1.22E‐04 |
| rs11665676 | 19 | 45378719 | NECTIN2;TOMM40:APOE | C | T | 18622 | 0.77 (0.7‐0.85) | 6.16E‐07 | 21 | 0.76 | 2.40E‐05 | 11355 | 0.7 (0.62‐0.8) | 1.33E‐07 | 21 | 0.69 | 9.76E‐07 | 7267 | 0.89 (0.75‐1.05) | 1.63E‐01 | 21 | 0.89 | 1.70E‐01 | 3.45E‐02 |
| Discordant loci with P ≤ 1E‐5 in the H2 carriers a.2 | ||||||||||||||||||||||||
| rs7356060 | 3 | 86238011 | CADM2;LINC02070 | A | T | 18424 | 1.13 (1.05‐1.21) | 4.39E‐04 | 21 | 1.12 | 7.63E‐04 | 11231 | 1.04 (0.95‐1.13) | 4.28E‐01 | 21 | 1.03 | 5.77E‐01 | 7193 | 1.29 (1.16‐1.43) | 3.99E‐06 | 21 | 1.29 | 7.64E‐06 | 1.67E‐03 |
| rs348732 | 4 | 85250583 | LOC101928978;NKX6‐1 | C | A | 18605 | 0.91 (0.88‐0.96) | 5.82E‐05 | 21 | 0.91 | 5.32E‐05 | 11342 | 0.96 (0.91‐1.02) | 1.47E‐01 | 21 | 0.96 | 1.46E‐01 | 7263 | 0.84 (0.79‐0.91) | 1.99E‐06 | 21 | 0.83 | 4.49E‐07 | 6.17E‐03 |
| rs1838973 | 4 | 5157262 | STK32B | G | A | 18586 | 1.26 (1.14‐1.4) | 1.40E‐05 | 21 | 1.26 | 2.19E‐05 | 11332 | 1.14 (1‐1.31) | 5.43E‐02 | 21 | 1.14 | 6.95E‐02 | 7254 | 1.46 (1.24‐1.72) | 5.46E‐06 | 20 | 1.56 | 1.27E‐05 | 2.28E‐02 |
| rs55712126 | 5 | 161528378 | GABRG2 | T | G | 18703 | 1.12 (0.99‐1.26) | 6.85E‐02 | 21 | 1.09 | 1.66E‐01 | 11412 | 0.9 (0.78‐1.05) | 1.85E‐01 | 20 | 0.89 | 1.36E‐01 | 7291 | 1.62 (1.33‐1.99) | 2.88E‐06 | 21 | 1.60 | 9.85E‐06 | 3.91E‐06 |
| rs77007065 | 11 | 2319730 | C11orf21 | G | A | 18743 | 0.93 (0.84‐1.03) | 1.79E‐01 | 21 | 0.94 | 3.07E‐01 | 11426 | 1.12 (0.99‐1.28) | 7.88E‐02 | 21 | 1.12 | 8.86E‐02 | 7317 | 0.68 (0.58‐0.81) | 9.78E‐06 | 20 | 0.70 | 8.35E‐05 | 5.62E‐06 |
| rs140869727 | 11 | 85751041 | PICALM;EED | G | A | 18516 | 1.11 (1.06‐1.17) | 5.00E‐05 | 21 | 1.12 | 3.79E‐04 | 11283 | 1.05 (0.98‐1.12) | 1.57E‐01 | 21 | 1.05 | 3.05E‐01 | 7233 | 1.22 (1.12‐1.33) | 3.00E‐06 | 21 | 1.23 | 2.38E‐06 | 4.51E‐03 |
This table shows the loci with AD risk associations of P ≤1E‐5 in only H2 non‐carriers (a.1) or H2 carriers (a.2). The H2 tagging variant rs8070723 was used to stratify study participants into H2 non‐carriers (H1H1) and H2 carriers (H1H2+H2H2). The table shows the top loci from the LD‐based clumping implemented in PLINK using an r2 threshold of 0.2 within 1000kb.
Loci with P ≤ 1E‐5 in H2 non‐carriers and P ≥ 0.05 in the in H2 carriers.
Loci with P ≤ 1E‐5 in H2 carriers and P ≥ 0.05 in the in H2 non‐carriers. Rs140869727 at the PICALM locus was clumped with rs17159904, but rs17159904 did not meet the P ≥ 0.05 threshold in the H2 non‐carriers. Therefore, the result from the former is shown.
Chromosome, position, alleles from the February 2009 (GRCh37/hg19) build.
Nearest gene(s) located within ±100 kb of the top SNP.
Unstratified contains all subjects from the 21 ADGC cohorts used for analysis.
Joint analysis performed with logistic regression in PLINK using as covariates age, sex, cohort and PC1‐3. N, number of subjects analyzed; OR, odds ratio; 95% CI, 95% confidence interval, P‐value.
Meta‐analysis of logistic regression analysis in PLINK using the random effects model, and using the covariates age, sex and PC1‐3. N, number of cohorts analyzed; OR, odds ratio, P‐value.
Epistasis analyses performed in R. All cohorts were combined and stratified into two groups by the H2 tagging variant rs8070723: H2 non‐carriers (H1H1) and H2 carriers (H1H2+H2H2). Results from the carrier model are shown.