Table 3.
Associations with diabetes incidence for internally replicated proteins that are specific to BMI or WHR (n = 4203)
| Proteins | Model 1a | Model 2b | Sensitivity analysisc | |||
|---|---|---|---|---|---|---|
| N | HR (95% CI) | FDR-adjusted P | HR (95% CI) | FDR-adjusted P | Adjusted P | |
| BMI | ||||||
| AM | 4131 | 1.16 (1.06, 1.27) | .0092 | 1.11 (1.01, 1.21) | .13 | .055 |
| GAL | 4131 | 0.93 (0.85, 1.01) | .27 | 0.95 (0.87, 1.03) | .36 | .32 |
| EMMPRIN | 4198 | 1.07 (0.98, 1.16) | .27 | 1.07 (0.99, 1.16) | .31 | .15 |
| KLK6 | 4131 | 0.95 (0.88, 1.04) | .34 | 0.96 (0.89, 1.05) | .44 | .45 |
| Gal3 | 4131 | 1.12 (1.03, 1.22) | .039 | 1.12 (1.03, 1.22) | .073 | .02 |
| hK11 | 4131 | 0.94 (0.87, 1.02) | .27 | 0.94 (0.87, 1.02) | .31 | .23 |
| MMP10 | 4131 | 0.95 (0.88, 1.04) | .34 | 0.95 (0.88, 1.04) | .36 | .35 |
| HE4 | 4198 | 1.03 (0.94, 1.12) | .52 | 1.04 (0.95, 1.13) | .50 | .55 |
| REG4 | 4198 | 0.97 (0.89, 1.05) | .45 | 0.98 (0.90, 1.06) | .54 | .62 |
| mAmP | 4131 | 1.06 (0.98, 1.15) | .28 | 1.06 (0.98, 1.15) | .31 | .24 |
| WHR | ||||||
| PRSS8 | 4198 | 1.29 (1.18, 1.42) | 3.09 × 10 –07 | 1.25 (1.15, 1.37) | 1.38 × 10 –05 | 1.22 × 10 –05 |
| IL18 | 4131 | 1.18 (1.09, 1.28) | .00034 | 1.14 (1.05, 1.24) | .0038 | .0073 |
| CCL20 | 4131 | 1.23 (1.14, 1.32) | 3.63 × 10 –07 | 1.20 (1.12, 1.30) | 1.38 × 10 –05 | 1.71 × 10 –05 |
| CCL4 | 4131 | 1.15 (1.07, 1.24) | .00053 | 1.13 (1.05, 1.22) | .0036 | .0071 |
| IL8 | 4131 | 1.15 (1.06, 1.24) | .00082 | 1.15 (1.06, 1.24) | .0016 | .0027 |
| CDKN1A | 4091 | 1.14 (1.05, 1.23) | .0023 | 1.11 (1.03, 1.21) | .011 | .023 |
| CXCL6 | 4131 | 1.19 (1.10, 1.29) | .00012 | 1.17 (1.08, 1.26) | .00093 | .0013 |
| CXCL11 | 4194 | 1.01 (0.93, 1.10) | .78 | 1.00 (0.92, 1.08) | .91 | .95 |
| GDF15 | 4131 | 1.20 (1.09, 1.31) | .00037 | 1.18 (1.08, 1.30) | .0016 | .0027 |
| CHI3L1 | 4131 | 1.14 (1.05, 1.24) | .0037 | 1.11 (1.02, 1.21) | .016 | .034 |
| CA125 | 4131 | 1.07 (0.98, 1.16) | .12 | 1.05 (0.97, 1.14) | .26 | .36 |
| LAPTGFbeta1 | 4198 | 1.17 (1.08, 1.27) | .00028 | 1.15 (1.06, 1.24) | .0016 | .0027 |
| CTSL1 | 4131 | 1.18 (1.08, 1.28) | .00037 | 1.14 (1.05, 1.24) | .0042 | .0090 |
| CASP3 | 4131 | 1.11 (1.02, 1.20) | .017 | 1.10 (1.01, 1.19) | .035 | .066 |
| CXCL5 | 4198 | 1.13 (1.04, 1.23) | .0044 | 1.12 (1.03, 1.22) | .012 | .025 |
| HBEGF | 4131 | 1.14 (1.06, 1.24) | .0016 | 1.13 (1.04, 1.22) | .0042 | .0090 |
| CXCL13 | 4128 | 1.10 (1.02, 1.19) | .022 | 1.08 (1.00, 1.17) | .064 | .11 |
| IL7 | 4149 | 1.15 (1.06, 1.24) | .00082 | 1.14 (1.05, 1.23) | .0031 | .0054 |
| Dkk1 | 4131 | 1.14 (1.05, 1.24) | .0021 | 1.14 (1.05, 1.24) | .0036 | .0071 |
| MMP7 | 4131 | 1.20 (1.10, 1.31) | .00016 | 1.21 (1.11, 1.32) | .00014 | .00022 |
| OPG | 4131 | 1.12 (1.02, 1.22) | .018 | 1.12 (1.03, 1.22) | .015 | .031 |
| SRC | 4131 | 0.94 (0.87, 1.02) | .13 | 0.94 (0.87, 1.02) | .13 | .19 |
Plasma proteins are standardized. Significant P values were highlighted in bold font.
Abbreviations: AM, Adrenomedullin; BMI, body mass index; CA125, Ovarian cancer-related tumor marker CA 125; CASP3, Caspase-3; CCL20, C-C motif chemokine 20; CCL4, C-C motif chemokine 4; CDKN1A, Cyclin-dependent kinase inhibitor 1; CHI3L1, Chitinase-3-like protein 1; CI, confidence interval; CTSL1, Cathepsin L1; CXCL11, C-X-C motif chemokine 11; CXCL13, C-X-C motif chemokine 13; CXCL5, C-X-C motif chemokine 5; CXCL6, C-X-C motif chemokine 6; Dkk1, Dickkopf-related protein 1; EMMPRIN, Extracellular matrix metalloproteinase inducer; FDR, false discovery rate; GAL, Galanin peptides; Gal3, Galectin-3; GDF15, Growth/differentiation factor 15; HBEGF, heparin binding epidermal growth factor like growth factor; HE4, Epididymal secretory protein E4; hK11, Kallikrein-11; HR, hazard ratio; IL18, Interleukin-18; IL7, Interleukin-7; IL8, Interleukin-8; KLK6, Kallikrein-6; LAPTGFbeta1, Latency-associated peptide transforming growth factor beta-1; mAmP, Membrane-bound aminopeptidase P; MMP10, Matrix metalloproteinase-10; MMP7, Matrix metalloproteinase-7; OPG, Osteoprotegerin; PRSS8, Prostasin; REG4, Regenerating islet-derived protein 4; SRC, Proto-oncogene tyrosine-protein kinase Src; WHR, waist-to-hip ratio. FDR-adjusted P < 0.05 was used as the cutoff.
a Cox proportional hazards regressions adjusted for age, sex, smoking, high alcohol consumption, systolic blood pressure, low density lipoprotein, and antihypertensive medication.
b Adjusted for covariates in Model 1 plus WHR or BMI.
c P values generated in multivariate analysis (Model 2) were corrected using a more strict FDR correction by taking all the protein–diabetes associations (multiple testing = 136 times) into consideration.