Table 1.
Association of mtDNA SNPs with global cognitive impairment during the progression of PD
| rCRS | Effect allele | Alternative allele | P | P a | HR (95% CI) | EAFb | EAF in European | EAF in East Asian | EAF in African |
|---|---|---|---|---|---|---|---|---|---|
| m.2706A>G | G | A | 2.46 × 10−5 | 0.003 | 0.68 (0.56–0.81) | 0.5826 | 0.5746 | 0.9960 | 0.9970 |
| m.14766C>T | T | C | 1.15 × 10−4 | 0.012 | 0.70 (0.58–0.84) | 0.5249 | 0.5169 | 0.9960 | 0.9985 |
| m.11251A>G | G | A | 0.002 | 0.204 | 0.67 (0.52–0.86) | 0.1942 | 0.1610 | 0.0000 | 0.0015 |
| m.15452C>A | A | C | 0.002 | 0.204 | 0.67 (0.52–0.87) | 0.1951 | 0.1610 | 0.0000 | 0.0000 |
| m.15607A>G | G | A | 0.017 | 1 | 0.65 (0.46–0.93) | 0.0984 | 0.0875 | 0.0000 | 0.0015 |
| m.16162A>G | G | A | 0.019 | 1 | 1.95 (1.12–3.40) | 0.0235 | 0.0199 | 0.0417 | 0.0015 |
| m.15928G>A | A | G | 0.021 | 1 | 0.66 (0.47–0.94) | 0.0998 | 0.0875 | 0.0080 | 0.0000 |
| m.11812A>G | G | A | 0.029 | 1 | 0.65 (0.44–0.96) | 0.0787 | 0.0696 | 0.0000 | 0.0045 |
| m.4917A>G | G | A | 0.030 | 1 | 0.66 (0.46–0.96) | 0.0971 | 0.0875 | 0.0000 | 0.0000 |
| m.9477G>A | A | G | 0.031 | 1 | 0.66 (0.46–0.96) | 0.0926 | 0.1392 | 0.0000 | 0.0061 |
| m.10589G>A | A | G | 0.041 | 1 | 1.89 (1.03–3.47) | 0.0110 | 0.0060 | 0.0020 | 0.0530 |
| m.16482A>G | G | A | 0.043 | 1 | 1.62 (1.02–2.59) | 0.0200 | 0.0139 | 0.0020 | 0.0000 |
| m.15218A>G | G | A | 0.045 | 1 | 0.55 (0.31–0.99) | 0.0453 | 0.0437 | 0.0119 | 0.0000 |
| m.10463T>C | C | T | 0.048 | 1 | 0.71 (0.51–1.00) | 0.1030 | 0.0875 | 0.0040 | 0.0000 |
P from the Cox proportional hazards statistic used to estimate the influence of SNP on time (years from onset of PD) to reaching the endpoint of GCI as indicated by a MMSE ≤ 25 in exploratory analyses using the combined population; age at onset of PD, sex, years of education and PHS (including GBA mutation status, APOE ε4 allele haplotype, and rs182987047, rs138073281 and rs8050111) were included as covariates in the Cox analyses. A ‘cohort’ term was included as a random effect. rCRS = revised Cambridge Reference Sequence.
Bonferroni correction based on the result of 102 mtDNA SNPs from combined analysis was performed using the p.adjust function with the ‘Bonferroni’ method in R.
Based on 4491 patients with PD across 15 cohorts. EAF in 503 European, 503 East Asian or 661 African was calculated based on dataset of Phase 1 and 3 of the 1000 Genome Project mitochondrial variants calling by the MToolBox pipeline. EAF = Effect allele frequency.