Table 1.
Cross-sectional association and meta-analysis of mtDNA CN with metabolic disease phenotypes
| Traits | Initial (TopMed, European ancestry) (N = 13,378) |
Validation (UK Biobank, European ancestry) (N = 381,470) |
Overall meta-analysis (N = 394,848) |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | Β | SE | p value | OR | 95% CI | β | SE | p value | OR | 95% CI | β | SE | p value | |
| Binary outcomes | |||||||||||||||
| Obesity | 1.10 | 1.05–1.15 | – | – | 1.0 × 10−4 | 1.14 | 1.13–1.15 | – | – | 9.1 × 10−237 | 1.14 | 1.13–1.15 | – | – | 5.6 × 10−238 |
| HTN | 1.08 | 1.03–1.12 | – | – | 1.2 × 10−3 | 1.06 | 1.05–1.07 | – | – | 3.8 × 10−48 | 1.06 | 1.05–1.07 | – | – | 2.8 × 10−50 |
| Diabetes | 1.22 | 1.13–1.30 | – | – | 2.8 × 10−8 | 1.03 | 1.02–1.05 | – | – | 1.0 × 10−4 | 1.04 | 1.03–1.06 | – | – | 3.6 × 10−7 |
| Hyperlipidemia | 1.03 | 0.99–1.08 | – | – | 0.13 | 1.08 | 1.07–1.09 | – | – | 2.2 × 10−56 | 1.08 | 1.07–1.09 | – | – | 6.3 × 10−56 |
| Continuous outcomes | |||||||||||||||
| BMI | – | – | 0.2 | 0.046 | 2.0 × 10−5 | – | – | 0.3 | 0.0077 | 2.1 × 10−332 | – | – | 0.3 | 0.0076 | 1.0 × 10−335 |
| DBP | – | – | 0.042 | 0.1 | 0.69 | – | – | 0.24 | 0.019 | 5.9 × 10−39 | – | – | 0.24 | 0.018 | 4.6 × 10−38 |
| SBP | – | – | 0.43 | 0.18 | 0.019 | – | – | 0.64 | 0.033 | 7.5 × 10−86 | – | – | 0.64 | 0.032 | 9.5 × 10−87 |
| FBG | – | – | 0.054 | 0.093 | 0.56 | – | – | 0.23 | 0.019 | 1.1 × 10−32 | – | – | 0.22 | 0.019 | 6.5 × 10−32 |
| HDL | – | – | −0.012 | 0.0025 | 2.9 × 10−6 | – | – | 0.0034 | 0.0004 | 3.0 × 10−17 | – | – | 0.003 | 0.0004 | 2.2 × 10−14 |
| LDL | – | – | −0.0075 | 0.0027 | 0.0058 | – | – | 0.0066 | 0.00047 | 1.7 × 10−43 | – | – | 0.0061 | 0.0005 | 1.7 × 10−39 |
| TRIG | – | – | 0.03 | 0.0045 | 2.5 × 10−11 | – | – | 0.021 | 0.00082 | 4.5 × 10−149 | – | – | 0.022 | 0.0008 | 2.9 × 10−158 |
The β estimates are in units of metabolic traits corresponding to 1 SD lower mtDNA CN. Association analysis of mtDNA CN with metabolic traits was performed in cohorts of European Americans in TOPMed and also in European-ancestry participants in UK Biobank. Meta-analysis with the fixed or random-effects inverse-variance method was applied to summarize the results. See also Tables S2–S4, S6, and S8 and Figures S4–S13.