Table 4.
Estimates of obesity risk (odds ratios) and discriminative power (ROCAUCs) for nine purported obesity-risk variants singly and in combination in non-diabetic individuals (n = 3885)
| Nearest gene | SNP | Risk allele (frequency) | OR | 95% CI | P | ROCAUC | PROCAUC |
|---|---|---|---|---|---|---|---|
| FTO | rs1121980 | A (0.42) | 1.15 | (1.05–1.25) | 0.002 | 0.5435 | 2.00 × 10−4 |
| SH2B1 | rs7498665 | C (0.40) | 1.13 | (1.04–1.24) | 0.007 | 0.5348 | 1.72 × 10−6 |
| MTCH2 | rs4752856 | T (0.37) | 1.12 | (1.03–1.23) | 0.009 | 0.5257 | 1.10 × 10−7 |
| MC4R | rs17782313 | C (0.26) | 1.11 | (1.00–1.22) | 0.042 | 0.5293 | 1.04 × 10−6 |
| NEGR1 | rs2815752 | A (0.58) | 1.10 | (1.01–1.20) | 0.028 | 0.5263 | 2.21 × 10−7 |
| GNPDA2 | rs10938397 | G (0.37) | 1.10 | (1.00–1.20) | 0.045 | 0.5157 | 2.45 × 10−8 |
| TMEM18 | rs6548238 | A (0.82) | 1.10 | (0.98–1.22) | 0.095 | 0.5278 | 7.00 × 10−8 |
| KCTD15 | rs11084753 | G (0.63) | 1.05 | (0.96–1.14) | 0.33 | 0.5087 | 3.57 × 10−7 |
| PCSK1 | rs6235 | C (0.30) | 1.05 | (0.96–1.16) | 0.30 | 0.5221 | 1.20 × 10−6 |
| GBS (SD units) | – | – | 1.13 | (1.06–1.21) | <0.001 | 0.5752 | 2.00 × 10−5 |
| GBS (5th versus 1st quintile) | – | – | 1.40 | (1.14–1.72) | 0.002* | – | – |
For the calculation of odds ratios (OR), obesity is defined according to WHO (13,14). The area under the receiver operator characteristic curves (ROCAUC) reported in the table are unadjusted. PROCAUC is the significance level of the test for difference between the ROCAUC for each single nucleotide polymorphism (SNP) or the genetic burden score (GBS) versus the ROCAUC for all SNPs (0.6147). These comparisons test the ability of each genetic predictor to discriminate between 353 obese (BMI >30 kg/m2) and 1370 normal weight (BMI 18.5–24.9 kg/m2) individuals. As described in the results, gene–sex interactions were observed for obesity (P = 0.02) at the MC4R locus. *P-value obtained by direct comparison of fifth versus first GBS quintiles, adjusted for age and sex (n = 1325).