Table 2.
Results of the European genome-wide association meta-analyses and replication in the de novo genotyped cohorts
| rsID | Chr:Position | Candidate/ closest gene | Alleles (EA/OA) | EAF | OR | 95% CI | P | I2 (%) | P het |
|---|---|---|---|---|---|---|---|---|---|
| 90th percentile cases versus all controls (Discovery) | |||||||||
| rs116362179 | 2:53,380,757 | − | T/C | 0.05 | 1.34 | 1.20–1.50 | 4.9 × 10−7 | 0 | 0.457 |
| rs7676745a | 4:8,565,547 | GPR78 | A/G | 0.04 | 0.67 | 0.57–0.77 | 4.3 × 10−8 | 0 | 0.462 |
| rs7754015 | 6:127,206,068 | − | G/T | 0.43 | 0.90 | 0.86–0.94 | 6.8 × 10−7 | 0 | 0.670 |
| rs35262860 | 8:55,478,909 | RP1 | GCT/G | 0.39 | 1.11 | 1.07–1.15 | 3.9 × 10−7 | 0 | 0.941 |
| rs3138136 | 12:56,117,570 | RDH5 | T/C | 0.10 | 0.83 | 0.77–0.89 | 5.4 × 10−7 | 14.5 | 0.284 |
| rs429358 | 19:45,411,941 | APOE | C/T | 0.13 | 0.60 | 0.56–0.64 | 1.3 × 10−56 | 54.3 | 0.004 |
| rs7412 | 19:45,412,079 | APOE | T/C | 0.09 | 1.28 | 1.19–1.37 | 2.4 × 10−11 | 0 | 0.619 |
| 90th percentile cases versus all controls (Replication) | |||||||||
| rs429358 | 19:45,411,941 | APOE | C/T | 0.45 | 0.40–0.51 | 5.2 × 10−36 | 85.4 | 0.009 | |
| rs7412 | 19:45,412,079 | APOE | T/C | 1.32 | 1.18–1.48 | 2.4 × 10−6 | 16.6 | 0.274 | |
| 99th percentile cases versus all controls (Discovery) | |||||||||
| rs3830412 | 3:124,397,321 | KALRN | A/AT | 0.22 | 1.21 | 1.12–1.30 | 4.3 × 10−7 | 0 | 0.767 |
| rs138762279 | 5:173,710,197 | − | AT/A | 0.16 | 0.79 | 0.72–0.86 | 1.2 × 10−7 | 0 | 0.769 |
| rs62502826 | 8:28,982,295 | KIF13B | A/G | 0.15 | 1.23 | 1.13–1.33 | 5.6 × 10−7 | 14.9 | 0.298 |
| rs7039467 | 9:22,056,213 | CDKN2A/B | A/G | 0.48 | 1.20 | 1.12–1.28 | 1.1 × 10−7 | 0 | 0.843 |
| rs429358 | 19:45,411,941 | APOE | C/T | 0.13 | 0.52 | 0.47–0.58 | 3.9 × 10−34 | 0 | 0.833 |
| rs7412 | 19:45,412,079 | APOE | T/C | 0.09 | 1.47 | 1.32–1.64 | 3.2 × 10−12 | 0 | 0.639 |
| 99th percentile cases versus all controls (Replication) | |||||||||
| rs429358 | 19:45,411,941 | APOE | C/T | 0.44 | 0.38–0.50 | 4.0 × 10−32 | 84.0 | 0.012 | |
| rs7412 | 19:45,412,079 | APOE | T/C | 1.35 | 1.19–1.53 | 2.0 × 10−6 | 0 | 0.534 | |
EA effect allele, OA other allele, EAF effect allele frequency, OR odds ratio (i.e., odds to become long-lived when carrying the effect allele); 95% CI 95% confidence interval, I2 heterogeneity statistic, Phet P-value for heterogeneity
aWe were not able to replicate the effect of this genetic variant, since there was no Taqman SNP Genotyping Assay available. We only report the most significant genetic variant for the loci with at least one variant with a P-value ≤ 1 × 10–6. The rsID is based on dbSNP build 150. The Chr:Position is based on Genome Reference Consortium Human Build 37 (GRCh37)