Table 4.
Adipose tissue gene-specific DNA methylation in relation to adiposity, the LEAP Project (select number of genes displayed; full list of all 101 genes available in Supplementary Table 2, available at IJE online)
| Median, CpG-specific effect size estimate (p-value)a per gene regionb |
|||
|---|---|---|---|
| Android:gynoid fat ratio | Android fat | Trunk:limb fat ratio | |
| ADAMTS4 | |||
| 5'UTR | 0.107 (5.6 × 10–6) | 0.036 (1.3 × 10–6) | 0.1 (2.0 × 10–6) |
| TSS1500 | 0.092 (2.1 × 10–4) | 0.027 (5.2 × 10–4) | 0.092 (3.3 × 10–5) |
| TSS200 | 0.143 (5.9 × 10–4) | 0.058 (1.9 × 10–5) | 0.136 (2.6 × 10–4) |
| 1stExon | 0.107 (5.6 × 10–6) | 0.036 (1.3 × 10–6) | 0.1 (2.0 × 10–6) |
| 3'UTR | 0.051 (0.04) | 0.02 (0.01) | 0.04 (0.07) |
| AGAP2 | |||
| TSS1500 | 0.024 (9.3 × 10–3) | 0.006 (3.3 × 10–3) | 0.013 (9.2 × 10–3) |
| TSS200 | 0.035 (8.6 × 10–3) | 0.019 (1.6 × 10–3) | 0.032 (0.03) |
| 1stExon | 0.117 (2.0 × 10–4) | 0.049 (7.9 × 10–7) | 0.118 (2.4 × 10–5) |
| Body | 0.137 (2.3 × 10–4) | 0.056 (2.8 × 10–6) | 0.126 (5.1 × 10–5) |
| 3'UTR | 0.201 (1.7 × 10–5) | 0.075 (2.9 × 10–7) | 0.163 (1.2 × 10–4) |
| ANGPT2 | |||
| 5'UTR | 0.124 (4.0 × 10–4) | 0.044 (7.4 × 10–5) | 0.128 (3.8 × 10–5) |
| TSS1500 | 0.088 (1.9 × 10–3) | 0.02 (0.03) | 0.063 (0.01) |
| TSS200 | 0.122 (3.27 × 10–4) | 0.046 (1.5 × 10–5) | 0.123 (4.3 × 10–5) |
| 1stExon | 0.142 (2.1 × 10–4) | 0.051 (3.7 × 10–5) | 0.143 (2.0 × 10–5) |
| Body | 0.106 (1.3 × 10–3) | 0.031 (2.1 × 10–3) | 0.091 (2.2 × 10–3) |
| ANGPT4 | |||
| 5'UTR | 0.145 (2.1 × 10–6) | 0.046 (1.5 × 10–6) | 0.157 (3.6 × 10–9) |
| TSS1500 | 0.132 (1.1 × 10–4) | 0.049 (4.4 × 10–6) | 0.151 (4.4 × 10–7) |
| TSS200 | 0.04 (2.7 × 10–4) | 0.01 (5.5 × 10–3) | 0.048 (1.7 × 10–7) |
| 1stExon | 0.145 (2.1 × 10–6) | 0.046 (1.5 × 10–6) | 0.157 (3.6 × 10–9) |
| Body | 0.024 (0.10) | 0.007 (0.07) | 0.021 (0.09) |
| AOC3 | |||
| 5'UTR | 0.15 (1.4 × 10–4) | 0.056 (4.6 × 10–6) | 0.147 (2.8 × 10–5) |
| TSS1500 | 0.052 (0.04) | 0.023 (1.4 × 10–3) | 0.047 (0.02) |
| TSS200 | 0.137 (8.3 × 10–5) | 0.053 (8.5 × 10–7) | 0.137 (9.3 × 10–6) |
| 1stExon | 0.15 (7.3 × 10–5) | 0.056 (1.8 × 10–6) | 0.147 (1.1 × 10–5) |
| Body | 0.187 (1.1 × 10–5) | 0.066 (8.4 × 10–7) | 0.186 (7.9 × 10–7) |
| 3'UTR | 0.076 (2.5 × 10–3) | 0.035 (4.8 × 10–6) | 0.066 (3.8 × 10–3) |
| AQP7 | |||
| 5'UTR | 0.108 (3.5 × 10–5) | 0.037 (5.5 × 10–6) | 0.117 (3.1 × 10–7) |
| 1stExon | 0.108 (3.4 × 10–5) | 0.037 (5.4 × 10–6) | 0.117 (3.1 × 10–7) |
| Body | 0.023 (0.19) | 0.006 (0.31) | 0.02 (0.19) |
| CETP | |||
| 5'UTR | 0.124 (7.6 × 10–5) | 0.039 (4.4 × 10–5) | 0.121 (5.4 × 10–6) |
| TSS1500 | 0.149 (6.8 × 10–5) | 0.045 (7.0 × 10–4) | 0.148 (4.5 × 10–6) |
| TSS200 | 0.098 (2.5 × 10–4) | 0.028 (1.2 × 10–3) | 0.099 (3.4 × 10–5) |
| 1stExon | 0.124 (7.6 × 10–5) | 0.039 (4.4 × 10–5) | 0.121 (5.4 × 10–6) |
| Body | 0.004 (0.44) | −0.002 (0.01) | 0.004 (0.14) |
| 3'UTR | 0.128 (3.2 × 10–7) | 0.032 (1.0 × 10–4) | 0.115 (2.9 × 10–7) |
| DOCK9 | |||
| 5'UTR | 0.215 (1.9 × 10–6) | 0.073 (1.9 × 10–7) | 0.196 (1.2 × 10–6) |
| TSS1500 | 0.052 (0.01) | 0.014 (0.20) | 0.053 (1.7 × 10–3) |
| TSS200 | 0.225 (8.7 × 10–6) | 0.077 (8.1 × 10–7) | 0.212 (2.8 × 10–6) |
| 1stExon | 0.107 (0.46) | 0.037 (0.46) | 0.098 (0.40) |
| Body | 0.027 (0.07) | 0.009 (0.04) | 0.034 (0.04) |
| 3'UTR | 0.006 (0.51) | 0.002 (0.25) | −2 × 10–5 (0.30) |
| HOXA3 | |||
| 5'UTR | 0.051 (0.13) | 0.017 (0.08) | 0.033 (0.25) |
| TSS1500 | 0.056 (0.13) | 0.019 (0.07) | 0.034 (0.28) |
| TSS200 | 0.251 (4.8 × 10–7) | 0.089 (3.6 × 10–9) | 0.213 (3.3 × 10–6) |
| 1stExon | 0.113 (4.3 × 10–5) | 0.044 (8.6 × 10–8) | 0.115 (2.3 × 10–6) |
| Body | 0.006 (0.04) | 0.001 (0.23) | 0.006 (0.03) |
| 3'UTR | 0.112 (2.6 × 10–3) | 0.028 (9.0 × 10–3) | 0.101 (9.6 × 10–4) |
| LIPE | |||
| 5'UTR | 0.21 (4.2 × 10–6) | 0.059 (5.6 × 10–5) | 0.208 (2.6 × 10–7) |
| TSS1500 | −0.001 (0.13) | 0.001 (0.30) | −0.001 (0.46) |
| TSS200 | 0.289 (4.9 × 10–7) | 0.09 (8.4 × 10–7) | 0.29 (1.1 × 10–8) |
| 1stExon | 0.21 (4.2 × 10–6) | 0.059 (5.6 × 10–5) | 0.208 (2.6 × 10–7) |
| Body | 0.082 (1.7 × 10–4) | 0.033 (4.9 × 10–5) | 0.066 (1.6 × 10–4) |
| 3'UTR | −0.005 (0.32) | −0.003 (0.09) | −0.007 (0.13) |
| SOD3 | |||
| 5'UTR | 0.079 (0.39) | 0.033 (0.06) | 0.075 (0.10) |
| TSS1500 | 0.054 (6.6 × 10–3) | 0.025 (4.1 × 10–4) | 0.068 (1.8 × 10–4) |
| TSS200 | 0.183 (6.7 × 10–6) | 0.064 (7.0 × 10–7) | 0.185 (3.7 × 10–7) |
| 1stExon | 0.155 (4.0 × 10–6) | 0.059 (1.1 × 10–8) | 0.152 (3.7 × 10–7) |
| Body | 0.027 (0.32) | 0.002 (0.52) | 0.022 (0.36) |
| 3'UTR | 0.018 (1.4 × 10–4) | 0.002 (0.16) | 0.017 (4.3 × 10–5) |
| TIMP4 | |||
| 5'UTR | 0.113 (1.6 × 10–5) | 0.026 (1.8 × 10–4) | 0.102 (1.5 × 10–5) |
| TSS1500 | 0.191 (2.7 × 10–7) | 0.064 (3.7 × 10–8) | 0.184 (2.3 × 10–8) |
| TSS200 | 0.137 (1.3 × 10–6) | 0.041 (4.8 × 10–6) | 0.123 (1.2 × 10–6) |
| 1stExon | 0.113 (1.6 × 10–5) | 0.026 (2.5 × 10–3) | 0.102 (3.0 × 10–5) |
| Body | 0.2 (0.01) | 0.043 (0.27) | 0.239 (1.6 × 10–4) |
| 3'UTR | 0.018 (0.12) | 0.006 (0.11) | 0.026 (0.01) |
UTR, untranslated region; TSS, transcription start site.
aFor each of the adiposity phenotypes (columns), results report the effect size estimate and nominal p-value for the CpG with the median nominal p-value in each gene region of the gene. Although analyses for the process of gene selection were based on models with DNA methylation on the M-value scale, once the top genes of interest were selected, results for the top genes were redone with methylation on the beta scale, in order to provide interpretable effect estimates in this table. Therefore, results displayed here are based on models with the adiposity phenotype of interest as exposure, DNA methylation (on the beta scale) as the outcome and adjusted for sex, race and current smoking.
bFor some genes, not all gene regions are displayed, as no CpGs (after applying our CpG exclusion criteria) were mapped to that gene region.