TABLE 1.
Unstratified f | H2 non‐carriers f | H2 carriers f | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SNP a | CHR c | Position c | Closest gene d | Major/Minor c | MAF e | Nj g | ORJ (95% CI) g | P J g | NM h | ORm h | PM h | Nj g | ORJ (95% CI) g | PJ g | NM h | ORm h | PM h | Nj g | ORJ (95% CI) g | PJ g | NM h | ORm h | PM h | Epistatis P i |
rs6656401 | 1 | 207692049 | CR1 | G/A | 0.183 | 17833 | 1.15 (1.08‐1.21) | 2.37E‐06 | 21 | 1.15 | 1.37E‐06 | 10854 | 1.13 (1.05‐1.21) | 9.82E‐04 | 21 | 1.14 | 7.48E‐04 | 6979 | 1.17 (1.07‐1.28) | 7.45E‐04 | 21 | 1.17 | 1.36E‐03 | 5.37E‐01 |
rs6733839 | 2 | 127892810 | BIN1;CYP27C1 | C/T | 0.394 | 14091 | 1.23 (1.17‐1.3) | 4.39E‐16 | 21 | 1.23 | 1.89E‐10 | 8627 | 1.23 (1.15‐1.31) | 2.64E‐10 | 21 | 1.23 | 1.25E‐09 | 5464 | 1.24 (1.14‐1.35) | 3.43E‐07 | 21 | 1.27 | 6.23E‐08 | 8.38E‐01 |
rs35349669 | 2 | 234068476 | INPP5D | C/T | 0.482 | 17273 | 1.04(1‐1.09) | 7.35E‐02 | 21 | 1.04 | 7.39E‐02 | 10535 | 1.04 (0.99‐1.11) | 1.37E‐01 | 21 | 1.05 | 9.74E‐02 | 6738 | 1.03 (0.96‐1.11) | 3.69E‐01 | 21 | 1.02 | 5.38E‐01 | 8.82E‐01 |
rs190982 | 5 | 88223420 | MEF2C‐AS1 | A/G | 0.384 | 16317 | 0.94 (0.9‐0.98) | 9.25E‐03 | 21 | 0.93 | 5.87E‐03 | 9911 | 0.93 (0.88‐0.99) | 2.53E‐02 | 21 | 0.92 | 1.03E‐02 | 6406 | 0.95 (0.88‐1.02) | 1.78E‐01 | 21 | 0.96 | 2.87E‐01 | 7.69E‐01 |
rs9271192 | 6 | 32578530 | HLA‐DRB1;HLA‐DQA1 | A/C | 0.272 | 18208 | 1.1 (1.05‐1.15) | 1.51E‐04 | 21 | 1.10 | 2.37E‐03 | 11080 | 1.14 (1.07‐1.21) | 7.56E‐05 | 21 | 1.14 | 1.85E‐03 | 7128 | 1.04 (0.96‐1.13) | 2.92E‐01 | 21 | 1.05 | 2.73E‐01 | 1.02E‐01 |
rs10948363 | 6 | 47487762 | CD2AP | A/G | 0.274 | 18827 | 1.09 (1.04‐1.14) | 5.18E‐04 | 21 | 1.09 | 5.22E‐04 | 11476 | 1.05 (0.98‐1.11) | 1.56E‐01 | 21 | 1.05 | 1.47E‐01 | 7351 | 1.16 (1.07‐1.25) | 1.60E‐04 | 21 | 1.16 | 6.81E‐04 | 3.47E‐02 |
rs2718058 | 7 | 37841534 | GPR141;NME8 | A/G | 0.364 | 18336 | 0.93 (0.89‐0.98) | 2.81E‐03 | 21 | 0.94 | 7.69E‐02 | 11182 | 0.94 (0.89‐1) | 4.77E‐02 | 21 | 0.97 | 3.96E‐01 | 7154 | 0.92 (0.86‐0.99) | 2.78E‐02 | 21 | 0.92 | 2.50E‐02 | 6.38E‐01 |
rs1476679 | 7 | 100004446 | ZCWPW1/PILRB | T/C | 0.280 | 18617 | 0.92 (0.88‐0.97) | 1.22E‐03 | 21 | 0.92 | 1.73E‐03 | 11346 | 0.88 (0.83‐0.94) | 7.06E‐05 | 21 | 0.88 | 8.06E‐05 | 7271 | 0.99 (0.92‐1.07) | 7.82E‐01 | 21 | 0.98 | 7.21E‐01 | 2.20E‐02 |
rs11771145 | 7 | 143110762 | EPHA1‐AS1 | G/A | 0.334 | 17291 | 0.93 (0.89‐0.97) | 1.97E‐03 | 21 | 0.93 | 4.22E‐03 | 10525 | 0.93 (0.88‐0.99) | 1.85E‐02 | 21 | 0.93 | 2.87E‐02 | 6766 | 0.93 (0.86‐1) | 4.27E‐02 | 21 | 0.93 | 6.38E‐02 | 8.76E‐01 |
rs28834970 | 8 | 27195121 | PTK2B | T/C | 0.363 | 18538 | 1.13 (1.08‐1.18) | 1.68E‐07 | 21 | 1.13 | 1.64E‐07 | 11305 | 1.14 (1.07‐1.2) | 1.48E‐05 | 21 | 1.14 | 1.67E‐04 | 7233 | 1.12 (1.04‐1.2) | 3.15E‐03 | 21 | 1.12 | 3.42E‐03 | 6.97E‐01 |
rs9331896 b | 8 | 27467686 | CLU | T/C | 0.377 | 16160 | 0.90 (0.86‐0.95) | 2.45E‐05 | NA | NA | NA | 9842 | 0.91 (0.85‐0.96) | 1.36E‐03 | NA | NA | NA | 6318 | 0.90 (0.84‐0.98) | 9.41E‐03 | NA | NA | NA | 9.87E‐01 |
rs10838725 | 11 | 47557871 | CELF1 | T/C | 0.316 | 18596 | 1.04 (0.99‐1.09) | 1.25E‐01 | 21 | 1.04 | 9.93E‐02 | 11334 | 1.04 (0.98‐1.11) | 1.63E‐01 | 21 | 1.04 | 2.03E‐01 | 7262 | 1.03 (0.96‐1.11) | 4.20E‐01 | 21 | 1.04 | 2.99E‐01 | 7.52E‐01 |
rs983392 | 11 | 59923508 | MS4A2;MS4A6A | A/G | 0.398 | 18095 | 0.87 (0.84‐0.91) | 2.44E‐09 | 21 | 0.87 | 5.14E‐09 | 11017 | 0.87 (0.83‐0.93) | 3.61E‐06 | 21 | 0.87 | 3.55E‐06 | 7078 | 0.87 (0.81‐0.93) | 1.11E‐04 | 21 | 0.86 | 4.95E‐03 | 9.28E‐01 |
rs10792832 | 11 | 85867875 | PICALM;EED | G/A | 0.355 | 18651 | 0.88 (0.84‐0.92) | 7.90E‐09 | 21 | 0.88 | 9.90E‐09 | 11368 | 0.89 (0.84‐0.94) | 3.32E‐05 | 21 | 0.89 | 7.71E‐05 | 7283 | 0.86 (0.8‐0.93) | 5.00E‐05 | 21 | 0.85 | 4.90E‐05 | 5.56E‐01 |
rs11218343 | 11 | 121435587 | SORL1 | T/C | 0.039 | 18816 | 0.76 (0.68‐0.84) | 7.44E‐07 | 21 | 0.75 | 9.94E‐07 | 11465 | 0.8 (0.69‐0.92) | 1.46E‐03 | 21 | 0.80 | 2.20E‐03 | 7351 | 0.69 (0.58‐0.83) | 5.43E‐05 | 18 | 0.69 | 1.34E‐04 | 2.26E‐01 |
rs17125944 | 14 | 53400629 | FERMT2 | T/C | 0.093 | 18809 | 1.12 (1.04‐1.21) | 2.75E‐03 | 21 | 1.13 | 2.59E‐02 | 11459 | 1.11 (1.01‐1.22) | 3.68E‐02 | 21 | 1.09 | 1.84E‐01 | 7350 | 1.15 (1.02‐1.29) | 2.38E‐02 | 21 | 1.15 | 2.32E‐02 | 5.89E‐01 |
rs10498633 | 14 | 92926952 | SLC24A4 | G/T | 0.217 | 18720 | 0.92 (0.88‐0.97) | 2.27E‐03 | 21 | 0.93 | 5.80E‐03 | 11409 | 0.9 (0.84‐0.96) | 1.45E‐03 | 21 | 0.90 | 2.50E‐03 | 7311 | 0.96 (0.88‐1.04) | 3.27E‐01 | 21 | 0.97 | 5.18E‐01 | 2.21E‐01 |
rs8093731 | 18 | 29088958 | DSG2 | C/T | 0.010 | 18683 | 0.94 (0.76‐1.16) | 5.49E‐01 | 20 | 1.01 | 9.39E‐01 | 11389 | 0.9 (0.69‐1.18) | 4.62E‐01 | 18 | 0.84 | 2.92E‐01 | 7294 | 0.99 (0.72‐1.38) | 9.70E‐01 | 15 | 1.14 | 6.31E‐01 | 6.37E‐01 |
rs4147929 b | 19 | 1063443 | ABCA7 | G/A | 0.171 | 16429 | 1.14 (1.07‐1.21) | 4.60E‐05 | NA | NA | NA | 10002 | 1.09 (1.01‐1.18) | 2.97E‐02 | NA | NA | NA | 6427 | 1.21 (1.09‐1.33) | 1.61E‐04 | NA | NA | NA | 1.34E‐01 |
rs3865444 | 19 | 51727962 | CD33 | C/A | 0.303 | 18707 | 0.91 (0.87‐0.96) | 1.78E‐04 | 21 | 0.91 | 1.70E‐04 | 11395 | 0.92 (0.87‐0.98) | 8.80E‐03 | 21 | 0.92 | 1.14E‐02 | 7312 | 0.9 (0.84‐0.97) | 6.84E‐03 | 21 | 0.89 | 3.35E‐03 | 6.27E‐01 |
rs7274581 | 20 | 55018260 | CASS4 | T/C | 0.084 | 18599 | 0.87 (0.8‐0.94) | 3.21E‐04 | 21 | 0.86 | 2.92E‐04 | 11333 | 0.88 (0.8‐0.98) | 1.71E‐02 | 21 | 0.88 | 2.01E‐02 | 7266 | 0.84 (0.74‐0.95) | 5.15E‐03 | 21 | 0.84 | 5.66E‐03 | 4.88E‐01 |
IGAP variants determined in the publication Lambert et al.21
SNPs rs4147929 and rs9331896 were filtered out of the original analysis due to the QC procedures in Boehme et al.27 They were evaluated separately for the joint analysis.
Chromosome, position, alleles from the February 2009 (GRCh37/hg19) build.
Nearest gene(s) located within ±100 kb of the IGAP SNP.
MAF calculated in PLINK derived from the unstratified genotypes.
Unstratified contains all subjects from the 21 ADGC cohorts used for analysis. The H2 tagging variant rs8070723 was used to stratify study participants into H2 non‐carriers (H1H1) and H2 carriers (H1H2+H2H2).
Joint analysis performed with logistic regression in PLINK using as covariates age, sex, cohort, and PC1‐3. Rs4147929 is missing in the GSK cohort. N, number of subjects analyzed; OR, odds ratio for AD risk for the minor allele; 95% CI, 95% confidence interval, P‐value.
Meta‐analysis performed with logistic regression analysis in PLINK using the random effects model, and using the covariates age, sex, and PC1‐3. Meta‐analysis could not be performed for rs4147929 and rs9331896. 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.