Table 1.
SNPs suggested to be associated with all statin‐induced myopathy and severe myopathy from the discovery case‐control analysis, replication analysis, independent simvastatin and cerivastatin study analyses, and the combined meta‐analysis
| All myopathy | Discovery case‐control study CPRD cases (n = 128) vs. WTCCC (n = 2,501) | Replication study EUDRAGENE cases (n = 19) vs. CPRD statin‐tolerant (n = 585) | Simvastatin validation case‐control study definite/incipient myopathy cases (n = 141) vs. controls (n = 4,046) | Cerivastatin validation case‐control study cases (n = 172) vs. controls (n = 361) | Combined meta‐analysis cases (n = 460) vs. controls (n = 7,493) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rs# | Chr | Gene | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | I 2 |
| rs36121096 | 5 | PDE4D | 3.82 (2.20–6.62) | 2.0 × 10−5 | 0 (0–∞) | 1.00 | 1.37 (0.56–6.07) | 0.61 | 1.51 (0.60–3.82) | 0.38 | 2.01 (1.22–3.31) | 0.006 | 0.00 |
| rs55902659 | 5 | SLC12A2 | 0.44 (0.31–0.66) | 4.9 × 10−6 | 0.42 (0.15–1.18) | 0.10 | 0.81 (0.76–1.90) | 0.24 | 1.00 (0.72–1.37) | 0.99 | 0.74 (0.59–0.92) | 0.008 | 0.84 |
| rs17359612 | 9 | TLE1 | 2.49 (1.71–3.64) | 1.1 × 10−5 | 1.59 (0.58–4.35) | 0.36 | 1.25 (0.51–4.17) | 0.54 | 1.21 (0.63–2.33) | 0.56 | 1.67 (1.19–2.34) | 0.003 | 0.00 |
| rs79860430 | 14 | ATG14 | 2.59 (1.76–3.82) | 8.4 × 10−6 | 0 (0–∞) | 1.00 | 1.13 (0.34–8.16) | 0.81 | 1.27 (0.62–2.58) | 0.51 | 2.17 (1.48–3.17) | 7.61 × 10‐5 | 0.53 |
| rs77855582 | 16 | GALNS | 3.88 (2.25–6.69) | 1.9 × 10−5 | 3.60 (0.99–13.0) | 0.05 | 1.61 (0.78–4.55) | 0.45 | NA | NA | NA | NA | NA |
| Severe myopathy | Discovery case‐control study CPRD cases (n = 32) vs. WTCCC (n = 2,501) | Replication study EUDRAGENE cases (n = 13) vs. CPRD statin‐tolerant (n = 585) | Simvastatin validation case‐control study definite myopathy cases (n = 54) vs. controls (n = 4,046) | Cerivastatin validation case‐control study cases (n = 172) vs. controls (n = 361) | Combined meta‐analysis cases (n = 271) vs. controls (n = 7,493) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rs# | Chr | Gene | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | Per allele OR (95% CI) | P value | I 2 |
| rs73089338 | 3 | CDCP1 | 4.63 (2.70–7.96) | 1.9 × 10−7 | 1.07 (0.25–4.54) | 0.92 | 0.70 (0.26–1.90) | 0.49 | 1.02 (0.49–2.16) | 0.95 | 1.94 (1.27–2.98) | 0.002 | 0.86 |
| rs504365 | 5 | RASGRF2 | 0.18 (0.07–0.44) | 2.9 × 10−6 | 1.63 (0.73–3.65) | 0.23 | 1.60 (0.99–2.57) | 0.06 | 1.28 (0.94–1.75) | 0.11 | 1.17 (0.92–1.50) | 0.20 | 0.82 |
| rs2247256 | 8 | ERICH1 | 0.16 (0.06–0.43) | 1.9 × 10−6 | 1.81 (0.80–4.07) | 0.15 | 0.58 (0.36–0.91) | 0.02 | 1.03 (0.76–1.40) | 0.85 | 0.78 (0.61–0.99) | 0.04 | 0.82 |
| rs117576073 | 11 | CYP2R1 | 8.36 (3.66–19.06) | 2.8 × 10−5 | 0 (0–∞) | 1.00 | 0.48 (0.03–8.68) | 0.62 | 0.31 (0.04–2.31) | 0.26 | 3.11 (1.25–7.78) | 0.01 | 0.79 |
| rs4149056 | 12 | SLCO1B1 | 5.15 (3.13–8.45) | 2.5 × 10 −9 | 3.98 (1.75–9.03) | 0.001 | 4.91 (3.09–7.77) | 1.3 × 10 −11 | 1.86 (1.32–2.62) | 3.9 × 10−4 | 2.99 (2.34–3.82) | 2.63 × 10 −18 | 0.87 |
| rs4149000 | 12 | SLCO1A2 | 3.94 (2.36–6.57) | 2.9 × 10−6 | 2.53 (1.00‐6.39) | 0.050 | 7.29 (4.13–12.8) | 6.5 × 10 −12 | 1.74 (1.16–2.60) | 0.007 | 2.81 (2.10–3.75) | 3.31 × 10 −12 | 0.91 |
| rs28447350 | 13 | Intergenic | 3.66 (2.23–6.00) | 5.3 × 10−7 | 0.55 (0.21–1.43) | 0.219 | 0.88 (0.49–1.59) | 0.676 | 1.06 (0.73–1.52) | 0.76 | 1.32 (1.01–1.74) | 0.04 | 0.84 |
Data indicates P values and ORs (95% CI; per‐allele) derived from logistic regression for discovery cohort vs. WTCCC cohort (n = 2,501). Only associations < 5 × 10−5 in the initial discovery cohort are shown with those reaching genomewide significance (P < 5 × 10−8) highlighted in bold.
CI, confidence interval; CPRD, Clinical Practice Research Datalink; NA, not available; OR, odds ratio; SNPs, single nucleotide polymorphisms; WTCCC, Wellcome Trust Case‐Control Consortium.