Background
Methods
Study sample
SNP genotyping
Age (at last visit or at Death) | All | Females | Males |
---|---|---|---|
PSP | |||
Mean (± SD) | 75 (± 7.6) | 76 (± 7.7) | 74 (± 7.4) |
Range (minimum-maximum) | 42 (54–96) | 36.8 (57–94) | 42 (54–96) |
Count | 533 | 240 | 293 |
Controls (All) | |||
Mean (± SD) | 77 (± 8.7) | 77 (± 8.7) | 76 (± 8.7) |
Range (minimum-maximum) | 71 (27–98) | 71 (27–98) | 64 (33–97) |
Count | 1172 | 557 | 615 |
Controls (Clinical) | |||
Age (at last visit) | |||
Mean (± SD) | 76 (± 8) | 76 (± 7.5) | 76 (± 8.4) |
Range (minimum-maximum) | 43 (54–97) | 39 (57–96) | 43 (54–97) |
Count | 1066 | 497 | 569 |
Controls (pathology) | |||
Age (at death) | |||
Mean (± SD) | 82 (± 12.9) | 82 (± 14.7) | 83 (± 10.3) |
Range (minimum-maximum) | 71 (27–98) | 71 (27–98) | 63 (33–96) |
Count | 106 | 60 | 46 |
Statistical analysis
Functional annotation
Results
GWAS Hoglinger et al. (EUR only) | New Mayo case-control population | Meta-analysis | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GWAS Stage 1 | GWAS Stage 2 | Joint Analysis | ||||||||||||||||
SNP ID | chr | GRCh38 location | Gene or nearby gene | Major allele | Minor allele | MAF cases | MAF control | MAF cases | MAF control | OR | PJ | MAF cases | MAF control | OR (95% CI) | P | OR (95% CI) | P | OR Direction |
rs8070723 | 17 | 46,003,698 | MAPT | A | G | 0.051 | 0.235 | 0.060 | 0.232 | 5.46 | 1.5E-116 | 0.049 | 0.233 | 5.74 (4.24–7.78) | 1.9E-29 | 5.51 (4.83–6.28) | 5.57E-144 | ++ |
rs242557 | 17 | 45,942,346 | MAPT | G | A | 0.530 | 0.348 | 0.495 | 0.355 | 0.51 | 4.2E-70 | 0.585 | 0.403 | 0.52 (0.45–0.61) | 1.2E-18 | 0.51 (0.48–0.55) | 3.78E-85 | – |
rs1768208 | 3 | 39,481,512 | MOBP | G | A | 0.357 | 0.286 | 0.353 | 0.287 | 0.72 | 1.0E-16 | 0.389 | 0.264 | 0.56 (0.48–0.66) | 6.6E-13 | 0.69 (0.64–0.74) | 3.48E-26 | – |
rs12203592 | 6 | 396,321 | IRF4 | C | T | 0.164 | 0.200 | 0.131 | 0.198 | 1.49 | 6.2E-15 | 0.159 | 0.173 | 1.09 (0.89–1.33) | 3.9E-01 | 1.40 (1.28–1.53) | 2.31E-13 | ++ |
rs7571971 | 2 | 88,595,833 | EIF2AK3 | C | T | 0.314 | 0.257 | 0.307 | 0.248 | 0.75 | 3.2E-13 | 0.320 | 0.291 | 0.88 (0.75–1.03) | 1.0E-01 | 0.77 (0.72–0.83) | 2.76E-13 | – |
rs1411478 | 1 | 180,993,146 | STX6 | G | A | 0.496 | 0.418 | 0.464 | 0.426 | 0.79 | 2.3E-10 | 0.473 | 0.410 | 0.77 (0.66–0.89) | 4.4E-04 | 0.79 (0.74–0.84) | 7.17E-13 | – |
rs11568563 | 12 | 21,304,500 | SLCO1A2 | A | C | 0.078 | 0.053 | 0.077 | 0.055 | 0.69 | 2.0E-07 | 0.089 | 0.053 | 0.60 (0.45–0.80) | 4.2E-04 | 0.67 (0.59–0.76) | 5.26E-10 | – |
rs6687758 | 1 | 221,991,606 | DUSP10 | A | G | 0.229 | 0.189 | 0.227 | 0.191 | 0.8 | 2.8E-07 | 0.230 | 0.192 | 0.80 (0.67–0.96) | 1.7E-02 | 0.80 (0.74–0.86) | 1.14E-08 | – |
rs197971 | 6 | 23,586,904 | LOC105374976 | G | A | 0.403 | 0.453 | 0.410 | 0.448 | 1.18 | 6.7E-06 | 0.395 | 0.422 | 1.13 (0.97–1.32) | 1.1E-01 | 1.17 (1.10–1.25) | 2.69E-06 | ++ |
rs2107272 | 7 | 43,156,788 | HECW1 | C | T | 0.342 | 0.296 | 0.325 | 0.301 | 0.85 | 3.6E-05 | 0.332 | 0.295 | 0.83 (0.71–0.98) | 2.5E-02 | 0.85 (0.79–0.91) | 3.04E-06 | – |
rs6846520 | 4 | 83,097,119 | PLAC8 | G | A | 0.071 | 0.109 | 0.089 | 0.108 | 1.35 | 3.9E-06 | 0.085 | 0.094 | 1.14 (0.88–1.47) | 3.3E-01 | 1.30 (1.16–1.46) | 4.87E-06 | ++ |
rs12744678 | 1 | 204,967,707 | NFASC | C | T | 0.331 | 0.280 | 0.302 | 0.287 | 0.86 | 2.1E-04 | 0.319 | 0.273 | 0.80 (0.68–0.94) | 5.6E-03 | 0.85 (0.79–0.91) | 6.22E-06 | – |
rs4733780 | 8 | 130,284,009 | ASAP1 | T | C | 0.454 | 0.423 | 0.446 | 0.414 | 0.86 | 3.2E-05 | 0.457 | 0.429 | 0.89 (0.77–1.03) | 1.1E-01 | 0.86 (0.81–0.92) | 9.94E-06 | – |
rs6852535 | 4 | 122,557,561 | IL2/IL21 | G | A | 0.289 | 0.338 | 0.277 | 0.322 | 1.24 | 9.2E-08 | 0.296 | 0.283 | 0.93 (0.79–1.09) | 3.8E-01 | 1.17 (1.09–1.26) | 1.11E-05 | +− |
rs10509119 | 10 | 60,052,882 | ANK3 | T | C | 0.131 | 0.110 | 0.133 | 0.112 | 0.80 | 4.1E-05 | 0.130 | 0.113 | 0.83 (0.67–1.04) | 1.1E-01 | 0.81 (0.73–0.89) | 1.29E-05 | – |
rs11902595 | 2 | 48,456,607 | PPP1R21 | T | G | 0.146 | 0.180 | 0.159 | 0.180 | 1.22 | 8.3E-05 | 0.161 | 0.184 | 1.21 (0.99–1.47) | 6.1E-02 | 1.21 (1.11–1.33) | 1.41E-05 | ++ |
rs2142991 | 10 | 42,845,657 | BMS1/ LOC101929445 | T | C | 0.139 | 0.173 | 0.139 | 0.169 | 1.30 | 4.9E-07 | 0.156 | 0.150 | 0.95 (0.77–1.16) | 6.0E-01 | 1.22 (1.11–1.34) | 2.13E-05 | +− |
rs406113 | 6 | 28,515,705 | GPX6 | T | G | 0.340 | 0.297 | 0.343 | 0.311 | 0.86 | 6.9E-05 | 0.339 | 0.314 | 0.90 (0.78–1.06) | 2.0E-01 | 0.87 (0.81–0.93) | 3.31E-05 | – |
rs4814911 | 20 | 19,863,250 | RIN2 | G | A | 0.225 | 0.190 | 0.212 | 0.193 | 0.84 | 7.7E-05 | 0.214 | 0.195 | 0.89 (0.75–1.07) | 2.3E-01 | 0.85 (0.78–0.92) | 4.40E-05 | – |
rs17199690 | 16 | 25,420,834 | LOC105371146 | G | A | 0.172 | 0.137 | 0.160 | 0.136 | 0.80 | 1.3E-05 | 0.144 | 0.139 | 0.97 (0.79–1.21) | 8.2E-01 | 0.83 (0.76–0.91) | 4.41E-05 | – |
rs895606 | 9 | 85,388,753 | NTRK2/ AGTPBP1 | C | T | 0.496 | 0.444 | 0.472 | 0.449 | 0.86 | 3.1E-05 | 0.475 | 0.465 | 0.96 (0.83–1.12) | 6.2E-01 | 0.88 (0.82–0.94) | 5.74E-05 | – |
rs11532787 | 7 | 119,661,732 | ANKRD7/KCND2 | G | A | 0.138 | 0.112 | 0.121 | 0.109 | 0.81 | 1.9E-04 | 0.116 | 0.102 | 0.86 (0.68–1.08) | 1.9E-01 | 0.82 (0.74–0.91) | 9.73E-05 | – |
rs3017756 | 11 | 95,804,194 | CEP57 | C | T | 0.482 | 0.426 | 0.438 | 0.429 | 0.86 | 6.6E-05 | 0.428 | 0.418 | 0.95 (0.82–1.10) | 5.0E-01 | 0.88 (0.82–0.94) | 9.96E-05 | – |
rs11028138 | 11 | 24,751,636 | LUZP2 | T | C | 0.102 | 0.081 | 0.085 | 0.068 | 0.75 | 6.8E-06 | 0.085 | 0.089 | 1.08 (0.83–1.41) | 5.7E-01 | 0.80 (0.71–0.90) | 1.42E-04 | −+ |
rs13025979 | 2 | 186,000,879 | LOC107985783 | C | T | 0.099 | 0.074 | 0.098 | 0.077 | 0.75 | 3.9E-06 | 0.080 | 0.088 | 1.15 (0.87–1.51) | 3.3E-01 | 0.80 (0.72–0.90) | 1.60E-04 | −+ |
rs10083119 | 12 | 125,824,612 | TMEM132B/ LOC101927464 | G | A | 0.126 | 0.096 | 0.119 | 0.103 | 0.80 | 8.0E-05 | 0.112 | 0.106 | 0.95 (0.75–1.20) | 6.6E-01 | 0.83 (0.75–0.91) | 2.07E-04 | – |
rs4890490 | 18 | 44,857,303 | SETBP1 | C | T | 0.436 | 0.385 | 0.413 | 0.402 | 0.88 | 9.0E-04 | 0.434 | 0.410 | 0.89 (0.77–1.03) | 1.2E-01 | 0.89 (0.83–0.95) | 2.76E-04 | – |
rs1433277 | 10 | 125,584,032 | TEX36 | G | T | 0.431 | 0.472 | 0.433 | 0.466 | 1.17 | 2.1E-05 | 0.460 | 0.450 | 0.96 (0.83–1.12) | 6.1E-01 | 1.13 (1.06–1.20) | 3.24E-04 | +− |
rs4256646 | 9 | 73,182,919 | ANXA1/ LOC101927281 | T | C | 0.458 | 0.509 | 0.466 | 0.490 | 1.16 | 9.6E-05 | 0.484 | 0.491 | 1.02 (0.88–1.18) | 8.1E-01 | 1.13 (1.06–1.20) | 3.33E-04 | ++ |
rs2075650 | 19 | 44,892,362 | TOMM40 | T | C | 0.112 | 0.141 | 0.117 | 0.140 | 1.26 | 2.8E-05 | 0.144 | 0.138 | 0.96 (0.77–1.19) | 6.9E-01 | 1.19 (1.08–1.32) | 3.99E-04 | +− |
rs9783599 | 14 | 77,970,692 | ADCK1 NRXN3 | C | A | 0.494 | 0.443 | 0.471 | 0.446 | 0.87 | 9.6E-05 | 0.469 | 0.475 | 1.05 (0.90–1.21) | 5.4E-01 | 0.90 (0.84–0.96) | 9.93E-04 | −+ |
rs4742987 | 9 | 106,119,937 | TMEM38B/ LOC100996590 | T | C | 0.393 | 0.359 | 0.389 | 0.364 | 0.86 | 6.8E-05 | 0.368 | 0.380 | 1.05 (0.90–1.22) | 5.1E-01 | 0.89 (0.84–0.96) | 1.08E-03 | −+ |
rs1001408 | 12 | 66,898,508 | GRIP1 | A | G | 0.119 | 0.086 | 0.103 | 0.095 | 0.81 | 5.1E-04 | 0.101 | 0.097 | 0.96 (0.76–1.23) | 7.7E-01 | 0.84 (0.75–0.93) | 1.15E-03 | – |
rs10197080 | 2 | 223,231,568 | KCNE4/RN7SL807P | G | T | 0.113 | 0.082 | 0.095 | 0.087 | 0.79 | 1.3E-04 | 0.100 | 0.104 | 1.08 (0.85–1.38) | 5.2E-01 | 0.84 (0.75–0.94) | 1.71E-03 | −+ |
rs4768559 | 12 | 44,576,131 | NELL2 | T | G | 0.262 | 0.209 | 0.224 | 0.214 | 0.85 | 2.1E-04 | 0.199 | 0.209 | 1.06 (0.89–1.28) | 5.1E-01 | 0.89 (0.82–0.96) | 1.77E-03 | −+ |
rs217727 | 11 | 1,995,678 | MRPL23/IGF2 | G | A | 0.218 | 0.178 | 0.189 | 0.177 | 0.85 | 3.5E-04 | 0.179 | 0.184 | 1.03 (0.85–1.24) | 7.9E-01 | 0.88 (0.81–0.95) | 2.02E-03 | −+ |
rs7104402 | 11 | 43,019,438 | LOC100507205/HNRNPKP3 | C | T | 0.323 | 0.281 | 0.302 | 0.290 | 0.87 | 6.2E-04 | 0.301 | 0.319 | 1.08 (0.92–1.27) | 3.4E-01 | 0.91 (0.85–0.98) | 8.58E-03 | −+ |
chr | GRCh38 location | r2 | D’ | SNP ID | SNP function annotation | Motifs | Regulome DB score |
---|---|---|---|---|---|---|---|
12 | 21,261,652 | 0.84 | 0.92 | rs188509290 | intergenic | Arid5a, Cdx, Cdx2, Dbx1, Foxa, Foxf1, Foxi1, Foxj2, Foxl1, HDAC2, Ncx, PLZF, Pou2f2, Pou3f4, TATA | 6 |
12 | 21,304,500 | 1 | 1 | rs11568563 | SLCO1A2 missense | Ets, NF-kappaB, Rad21 | 6 |
12 | 21,312,146 | 1 | 1 | rs145667214 | SLCO1A2 intronic | – | ND |
12 | 21,314,281 | 1 | −1 | rs7966334 | SLCO1A2 intronic | BATF, Irf, LBP-9, SRF | ND |
12 | 21,323,155 | 1 | 1 | rs74651308 | SLCO1A2 intronic | CEBPB, Evi-1, Hltf, Mef2, NF-E2, PLZF | ND |
12 | 21,332,593 | 0.98 | 1 | rs79424089 | SLCO1A2 intronic | Nkx2 | ND |
chr | GRCh38 location | r2 | D’ | SNP ID | SNP function annotation | Motifs | Regulome DB score |
---|---|---|---|---|---|---|---|
1 | 221,939,292 | 0.81 | 0.91 | rs17011141 | intergenic | DMRT1 | 5 |
1 | 221,940,306 | 0.81 | 0.91 | rs17011146 | intergenic | Barx2, Cdx2, Cdx2, Dbx2, Foxf1, Foxj1, Foxo, Hlx1, Hmx, Hoxa10, Hoxa9, Hoxb13, Hoxb9, Hoxc9, Hoxd8, Myc, Ncx, Nkx6–1, PLZF, Sox | 6 |
1 | 221,940,827 | 0.81 | 0.91 | rs72740077 | intergenic | COMP1, PPAR, RXR::LXR, RXRA, RXRA | 5 |
1 | 221,943,856 | 0.81 | 0.91 | rs7520544 | intergenic | Irf, Pax-5 | ND |
1 | 221,948,533 | 0.8 | 0.91 | rs12123928 | intergenic | Egr-1, Pax-2 | 6 |
1 | 221,952,186 | 0.81 | 0.91 | rs12137323 | intergenic | – | 7 |
1 | 221,954,218 | 0.81 | 0.91 | rs138207318 | intergenic | Zic | ND |
1 | 221,967,912 | 0.82 | 0.91 | rs148737902 | intergenic | – | ND |
1 | 221,974,208 | 1 | 1 | rs371061408 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | ND |
1 | 221,974,503 | 0.89 | 0.97 | rs12024555 | intronic RP11-815 M8.1 and RP11-400 N13.2 | EWSR1-FLI1, Zbtb3 | 7 |
1 | 221,974,877 | 0.89 | 0.96 | rs149685934 | intergenic | CACD, Pou1f1 | 6 |
1 | 221,975,001 | 0.911 | 1 | rs12025420 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 6 |
1 | 221,975,210 | 0.884 | 1 | rs12032598 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 5 |
1 | 221,975,457 | 0.94 | 0.98 | rs12032653 | intronic RP11-815 M8.1 and RP11-400 N13.2 | LF-A1 | 5 |
1 | 221,975,480 | 0.94 | 0.98 | rs12029332 | intronic RP11-815 M8.1 and RP11-400 N13.2 | BCL, NRSF | 5 |
1 | 221,975,548 | 0.92 | 0.98 | rs12025565 | intronic RP11-815 M8.1 and RP11-400 N13.2 | CAC-binding-protein, EWSR1-FLI1, Ets, Pax-3 | 6 |
1 | 221,975,629 | 0.88 | 0.98 | rs12032715 | intronic RP11-815 M8.1 and RP11-400 N13.2 | Foxo, GR, Nanog, Sox | 6 |
1 | 221,975,908 | 0.937 | 1 | rs144092743 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 7 |
1 | 221,975,912 | 0.937 | 1 | rs146528420 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 7 |
1 | 221,975,917 | 0.937 | 1 | rs141093369 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 6 |
1 | 221,976,623 | 1 | 1 | rs12026659 | intronic RP11-815 M8.1 and RP11-400 N13.2 | – | 7 |
1 | 221,980,119 | 0.94 | 0.98 | rs12129860 | intronic RP11-400 N13.2 | AP-2, Maf, Zbtb3 | 7 |
1 | 221,981,726 | 0.99 | 1 | rs12033415 | intronic RP11-400 N13.2 | – | 5 |
1 | 221,985,808 | 0.99 | 1 | rs12140604 | intergenic | Esr2, GATA, RORalpha1, Zbtb3 | 5 |
1 | 221,986,027 - 221,986,055 | 1 | 1 | rs138253686 | intergenic | – | 7 |
1 | 221,988,647 | 1 | 1 | rs6695584 | intergenic | PPAR, RXRA | 5 |
1 | 221,989,031 | 1 | 1 | rs6691195 | intergenic | – | ND |
1 | 221,990,985 | 0.99 | 1 | rs17011182 | intergenic | Hlx1, Hoxa9, Nanog, Pou4f3, Sox | 5 |
1 | 221,991,606 | 1 | 1 | rs6687758 | intergenic | Cdx2, Foxf1, Foxl1, Pou2f2, Pou3f3, TATA | 5 |
1 | 221,995,092 | 0.97 | 1 | rs12125383 | intergenic | Nanog, Pou5f1, Pou5f1 | 4 |
1 | 221,996,081 | 0.92 | 0.99 | rs34280100 | intergenic | AP-1, AP-2, ATF3, BCL, BHLHE40, CCNT2, CHD2, E2F, EBF, Egr-1, Ets, GR, HEN1, Irf, Klf4, Klf7, MAZ, MAZR, MOVO-B, Myc, NRSF, Nrf1, PLAG1, Pax-4, Pou2f2, RREB-1, SP1, SRF, STAT, Sp4, TATA, UF1H3BETA, WT1, YY1, ZNF219, Zfp281, Zfp740, Znf143 | 5 |
1 | 222,002,851-222,002,852 | 0.939 | 1 | rs141044286 | intergenic | – | 6 |
1 | 222,004,252-222,004,253 | 1 | 1 | rs552801974 | intergenic | – | NF |
1 | 222,005,490-222,005,491 | 0.939 | 1 | rs72221064 | intergenic | – | 6 |
1 | 222,006,808 | 0.94 | 0.99 | rs17442058 | intergenic | Hand1, Hoxa9, Hoxb13, Hoxb9, Hoxd10, Mef2, SP1, YY1, Zfp105 | 2b |
1 | 222,009,847 | 0.92 | 0.98 | rs12739936 | intergenic | Zbtb3 | 7 |
1 | 222,013,781 | 0.92 | 0.98 | rs11118926 | intergenic | Egr-1, Ets, MZF1::1–4, Nrf-2, Nrf1, Pax-5, TATA | 5 |
1 | 222,015,280 | 0.92 | 0.98 | rs35805428 | intergenic | Bcl6b, Hoxb6, STAT | 7 |
1 | 222,016,251 | 0.92 | 0.98 | rs17495159 | intergenic | CEBPA, CEBPB | 6 |
1 | 222,016,322 | 0.92 | 0.98 | rs35212520 | intergenic | YY1 | 6 |
1 | 222,016,779 | 0.92 | 0.98 | rs12731064 | intergenic | EBF, Elf5 | 7 |
1 | 222,018,163 | 0.92 | 0.98 | rs17011200 | intergenic | CDP, E2F, Evi-1, Smad3 | 5 |
1 | 222,018,592 | 0.92 | 0.98 | rs66666316 | intergenic | AP-1, Egr-1, Ets, Glis2, MAZR, MOVO-B, Myc, Pax-4, RREB-1, SP1, SRF, UF1H3BETA, YY1, ZNF219, Zfp281, Zfp740 | 6 |
1 | 222,019,622 | 0.92 | 0.98 | rs17442323 | intergenic | CTCF | 7 |
1 | 222,021,538 | 0.92 | 0.98 | rs12121134 | intergenic | Myc | 7 |
1 | 222,024,527 | 0.91 | 0.97 | rs56170536 | intergenic | NF-AT, SPIB, TATA, ZEB1, p300 | 5 |
1 | 222,025,330 | 0.91 | 0.97 | rs12125368 | intergenic | RORalpha1, RXRA | 7 |
1 | 222,026,325 | 0.91 | 0.97 | rs66732677 | intergenic | HNF1, Pbx-1, RFX5 | ND |
1 | 222,034,659-222,034,660 | 0.911 | 1 | rs71167281 | intergenic | – | ND |
1 | 222,045,419 | 0.84 | 0.96 | rs12135286 | intergenic | EBF, Nkx2, PPAR | 5 |
1 | 222,046,411 | 0.85 | 0.96 | rs35718308 | intergenic | Mef2, ZBTB33 | 7 |