Table 2.
Summary of current common variant (MAF ≥ 0.01) AD genomics findings from the GWAS by Jansen et al (14) and Kunkle et al (16)
| Chr | Pos | LeadSNP | A1 vs. A2 | MAF‡ | P‐value Jansen et al | P‐value Kunkle et al | AD effect | Nearest gene | AD pathway | Potential link to AD pathogenesis |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 161155392 | rs4575098 | A vs. G | 0.240 | 2.05E‐10 | 2.34E‐02* | Risk | ADAMTS4 | None | Neuroprotection: Extracellular Matric Protease |
| 1 | 207786828 | rs2093760 | A vs. G | 0.225 | 1.10E‐18 | 1.66E‐15* | Risk | CR1 | Immune | Innate Immunity; Neuroinflammation |
| 2 | 127891427 | rs4663105 | A vs. C | 0.412 | 3.38E‐44 | 2.16E‐26* | Risk | BIN1 | Lipid | Cellular Protein Trafficking |
| 2 | 233981912 | rs10933431 | G vs. C | 0.240 | 8.92E‐10 | 3.42E‐09** | Protection | INPPD5 | None | Autophagy; Viral Infection |
| 4 | 11026028 | rs6448453 | A vs. G | 0.228 | 1.93E‐09 | 4.90E‐05* | Risk | CLNK | None | Innate Immunity; Neuroinflammation |
| 6 | 32583357 | rs9469112 | T vs. A | 0.153 | 8.41E‐11 | 2.32E‐07** | Protection | HLA‐DRB1 | Immune | Adaptive Immunity |
| 6 | 47432637 | rs9381563 | C vs. T | 0.344 | 2.52E‐10 | 3.57E‐10** | Risk | CD2AP | None | Blood Brain Barrier; Aβ Transcytosis |
| 7 | 99971834 | rs4727449rs1859788 | A vs. G | 0.323 | 2.22E‐15 | 1.22E‐09** | Protection | ZCWPW1 | None | Innate Immunity; Neuroinflammation |
| 7 | 143108158 | rs7810606 | T vs. C | 0.425 | 3.59E‐11 | 1.13E‐06** | Protection | EPHA1 | None | Signal Transduction |
| 8 | 27464929 | rs28834970/rs4236673 | A vs. G | 0.390 | 2.61E‐19 | 5.60E‐23** | Protection | CLU/PTK2B | Immune; lipid; tau | Aβ clearance/SignalTransduction |
| 10 | 11717397 | rs11257238 | C vs. T | 0.382 | 1.26E‐08 | 2.61E‐07** | Risk | ECHDC3 | None | Lipid Metabolism |
| 11† | 47380340 | rs3740688 | G vs. T | 0.458 | 4.50E‐05 | 5.46E‐13** | Protection | SPI1/CELF1 | Immune | Potential false‐positive result (not replicated in UKB) |
| 11 | 59958380 | rs2081545 | A vs. C | 0.342 | 1.55E‐15 | 5.35E‐17** | Protection | MS4A6A | Immune | Innate Immunity; Neuroinflammation |
| 11 | 85776544 | rs867611 | G vs. A | 0.342 | 2.19E‐18 | 3.41E‐19** | Protection | PICALM | APP | Blood Brain Barrier; Aβ Transcytosis |
| 11 | 121435587 | rs11218343 | C vs. T | 0.035 | 1.09E‐11 | 2.88E‐12** | Protection | SORL1 | Lipid; APP | Cellular Protein Trafficking |
| 14† | 53391680 | rs17125924 | G vs. A | 0.099 | 5.26E‐06 | 1.42E‐09** | Protection | FERMT2 | n.a. | Potential false‐positive result (not replicated in UKB) |
| 14 | 92938855 | rs12590654 | A vs. G | 0.347 | 1.65E‐10 | 8.73E‐09* | Protection | SLC24A4 | None | Calcium Homeostasis |
| 15 | 59022615 | rs442495 | C vs. T | 0.334 | 1.31E‐09 | 2.51E‐7** | Protection | ADAM10 | Immune | Sheddase; APP Processing |
| 15 | 63569902 | rs117618017 | T vs. C | 0.132 | 3.35E‐08 | 2.38E‐04* | Risk | APH1B | None | γ‐secretase; APP Processing |
| 16 * | 19808163 | rs7185636 | C vs. T | 0.156 | 1.40E‐01 | 2.4E‐08 *** | Protection | IQCK | n.a. | Likely false‐positive result (not replicated in Jansen) |
| 16 | 31133100 | rs59735493 | A vs. G | 0.324 | 3.98E‐08 | 7.42‐03* | Protection | KAT8 | None | Transcriptional Regulation |
| 16 * | 79355857 | rs62039712 | G vs. A | 0.094 | 7.66E‐01 | 3.70E08 * | Risk | WWOX | n.a. | Likely false‐positive result (not replicated in Jansen) |
| 17 | 5138980 | rs113260531 | A vs. G | 0.118 | 9.16E‐10 | 3.70E‐04** | Risk | SCIMP | None | Innate Immunity; Neuroinflammation |
| 17 | 47450775 | rs28394864 | A vs. G | 0.471 | 1.87E‐08 | 4.85E‐03* | Risk | ABI3 | None | Innate Immunity; Neuroinflammation |
| 17 | 61538148 | rs138190086 | A vs. G | 0.017 | 2.65E‐04 | 5.30E‐09*** | Risk | ACE | Immune | Aβ degradation; blood pressure regulation |
| 18 | 56189459 | rs76726049 | C vs. T | 0.011 | 3.30E‐08 | 1.76E‐01* | Risk | ALPK2 | None | Signal Transduction |
| 19 | 1039323 | rs111278892 | G vs. C | 0.165 | 7.93E‐11 | 1.10E‐07* | Risk | ABCA7 | Lipid; APP | Lipid Metabolism; Innate Immunity |
| 19 | 45411941 | rs429358 | C vs. T | 0.155 | <1E‐900 | 1.17E‐881* | Risk | APOE | Lipid; APP; tau | Aβ clearance/Lipid Metabolism |
| 19 | 46241841 | rs76320948 | T vs. C | 0.059 | 4.64E‐08 | 1.22E‐04* | Risk | AC074212.3 | None | ? |
| 19 | 51727962 | rs3865444 | A vs. C | 0.336 | 6.34E‐09 | 5.27E‐06** | Protection | CD33 | None | Innate Immunity; Neuroinflammation |
| 20 | 54998544 | rs6014724 | G vs. A | 0.089 | 6.56E‐10 | 3.65E‐07* | Protection | CASS4 | None | Signal Transduction |
| 21 * | 28156856 | rs2830500 | A vs. C | 0.336 | 1.65E‐02 | 2.60E‐08 *** | Protection | ADAMTS1 | n.a. | Likely false‐positive result (not replicated in Jansen) |
“Chr,” “Pos,” “A1 vs. A2,” “AD effect” taken from Jansen et al. “Nearest gene” determined from UCSC genome browser (GRCh37; hg19).
Blue highlight indicates "novel" finding in GWAS by Jansen et al, grey highlight indicates "novel" findings in GWAS by Kunkle et al, no highlight indicates previously described GWAS findings.
AD pathway as determined in either or both GWAS: “immune” = “immune system response”; “lipid” = “lipid metabolism”, “APP” = “APP metabolism”, “tau” = “tau protein binding” (see text for more details).
“Potential link to AD pathogenesis” = based on the authors' review (and interpretation) of the literature.
Stage 1 result from Kunkle et al.
Stage 2 result from Kunkle et al.
Stage 3 result from Kunkle et al.
SPI1/CELF and FERMT2 represent results featured in Kunkle et al that poorly replicate in the UKB portion of Jansen et al; these are interpreted as possibly false‐positives here.
MAF = minor allele frequency; from European controls (non‐Finnish) as provided on GnomAD [v.2.1.1.; https://gnomad.broadinstitute.org/].
IQCK, WWOX, and ADAMTS1 represent results featured in Kunkle et al that are not replicated at P‐value < 0.01 in Jansen et al; these are interpreted as possibly false‐positives here.