Background
Methods
Study population
CpG methylation analysis
SNP genotyping
Statistical analyses
Bioinformatic analyses
Results
Characteristics of subjects
Study population | Methylation sub-population | |||
---|---|---|---|---|
MS+ | MS− | MS+ | MS− | |
Number of subjects | 1402 | 315 | 25 | 23 |
Age (years) | 43.9 ± 10.5 | 38.7 ± 9.8*** | 33.9 ± 9.4 | 32.0 ± 7.9 |
BMI (kg/m2) | 51.8 ± 8.5 | 51.3 ± 8.7 | 52.6 ± 12.7 | 52.3 ± 8.4 |
Waist girth (cm) | 141.5 ± 17.2 | 135.6 ± 18.5*** | 149.4 ± 24.8 | 143.3 ± 17.1 |
Fasting glucose (mmol/L) | 6.85 ± 2.43 | 5.11 ± 0.98*** | 6.61 ± 2.79 | 4.95 ± 0.46** |
Lipid profile (mmol/L) | ||||
Total-C | 4.67 ± 0.96 | 4.80 ± 0.82* | 4.93 ± 0.75 | 4.47 ± 0.87** |
LDL-C | 2.65 ± 0.83 | 2.79 ± 0.75** | 2.89 ± 0.65 | 2.68 ± 0.77 |
HDL-C | 1.18 ± 0.32 | 1.49 ± 0.37*** | 0.96 ± 0.19 | 1.28 ± 0.17*** |
TG | 1.97 ± 1.12 | 1.17 ± 0.37*** | 2.40 ± 1.30 | 1.12 ± 0.45*** |
Total-C/HDL-C | 4.18 ± 1.34 | 3.33 ± 0.74*** | 5.32 ± 1.49 | 3.51 ± 0.56*** |
Blood pressure (mm Hg) | ||||
SBP | 139 ± 16.7 | 134.7 ± 15.7*** | 145 ± 19.8 | 130.8 ± 13.2** |
DBP | 84 ± 11.3 | 83.0 ± 10.3 | 89 ± 12.0 | 78.0 ± 9.7** |
Methylation profile of TOMM20 locus
SNP genotyping and imputation
Identification of TOMM20 meQTL
Association between TOMM20 meQTLs and MS-related metabolic traits
Diplotype-based phenotype associations
Haplotypes (H) | rs4567344 (A > G) | rs11301 (T > C) | rs4551650 (G > A) | rs17523127 (G > C) | Frequency (%) |
---|---|---|---|---|---|
H1 | 0 | 0 | 1 | 1 | 25.3 |
H2 | 1 | 0 | 1 | 1 | 10.1 |
H3 | 1 | 1 | 1 | 1 | 35.1 |
H4 | 1 | 1 | 0 | 0 | 29.5 |
Diplotypes | |||||
H1/H1 | 0/0 | 0/0 | 1/1 | 1/1 | 6.6 |
H1/H2 | 0/1 | 0/0 | 1/1 | 1/1 | 5.1 |
H1/H3 | 0/1 | 0/1 | 1/1 | 1/1 | 18.0 |
H1/H4 | 0/1 | 0/1 | 1/0 | 1/0 | 14.4 |
H2/H2 | 1/1 | 0/0 | 1/1 | 1/1 | 0.7 |
H2/H3 | 1/1 | 0/1 | 1/1 | 1/1 | 7.2 |
H2/H4 | 1/1 | 0/1 | 1/0 | 1/0 | 6.3 |
H3/H3a
| 1/1 | 1/1 | 1/1 | 1/1 | 12.0 |
H3/H4 | 1/1 | 1/1 | 1/0 | 1/0 | 21.2 |
H4/H4 | 1/1 | 1/1 | 0/0 | 0/0 | 8.6 |
All | Men | Women | |||||
---|---|---|---|---|---|---|---|
Wald χ2 (P value) | OR (95 % CI) | Wald χ2 (P value) | OR (95 % CI) | Wald χ2 (P value) | OR (95 % CI) | ||
Total-C | H1/H2 | 5.9 (0.01) | 2.03 (1.59–3.59) | 4.7 (0.03) | 3.00 (1.11–8.06) | 1.7 (0.19) | 1.60 (0.79–3–24) |
H1/H3 | 1.5 (0.23) | 1.29 (0.85–1.96) | 4.3 (0.04) | 2.10 (1.04–4.25) | 0.0 (0.99) | 1.00 (0.60–1.68) | |
LDL–C | H1/H2 | 4.6 (0.03) | 1.86 (1.06–3.27) | 6.2 (0.01) | 3.54 (1.31–9.58) | 0.6 (0.45) | 1.31 (0.65–2.62) |
H1/H3 | 1.9 (0.17) | 1.34 (0.89–2.02) | 7.1 (0.008) | 2.64 (1.29–5.41) | 0.1 (0.80) | 0.94 (0.57–1.55) | |
TG | H1/H2 | 8.1 (0.004) | 2.19 (1.28–3.74) | 9.8 (0.002) | 7.02 (2.07–13.76) | 1.4 (0.24) | 1.46 (0.78–272) |
H1/H3 | 3.3 (0.03) | 1.53 (1.03–2.26) | 6.1 (0.01) | 2.43 (1.20–4.93) | 0.3 (0.57) | 1.14 (0.73–1.78) |