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. 2023 Feb 7;72(5):666–673. doi: 10.2337/db22-0628

Table 1.

Plasma proteins associated with incident type 2 diabetes in CHS after full covariate adjustment

UniProt identifier Gene symbol Target protein name HR (95% CI) P value Also associated with Prior evidence†
Glucose* IVGTT‡
Q9BRK3 MXRA8 Matrix-remodeling-associated protein 8 0.65 (0.57–0.73) 1.8 × 10−12 Yes SI, AIRG, DI, SG Yes
Q92729 PTPRU Receptor-type tyrosine-protein phosphatase U 1.32 (1.21–1.43) 2.4 × 10−11 No SI, DI, SG Yes
P08236 GUSB β-glucuronidase 1.46 (1.30–1.63) 2.5 × 10−11 Yes SI, DI, SG No
P42785 PRCP Lysosomal Pro-X carboxypeptidase 1.46 (1.31–1.64) 5.4 × 10−11 Yes SI, DI Yes
Q03154 ACY1 Aminoacylase-1 1.36 (1.24–1.48) 5.6 × 10−11 No SI, AIRG, DI Yes
Q13790 APOF Apolipoprotein F 0.68 (0.61–0.77) 7.2 × 10−11 Yes SI, AIRG, DI Yes
P18065 IGFBP2 Insulin-like growth factor–binding protein 2 0.66 (0.58–0.75) 2.8 × 10−10 Yes SI, AIRG, DI Yes
Q15848 ADIPOQ Adiponectin 0.68 (0.61–0.77) 4.0 × 10−10 Yes SI, DI, SG Yes
P52758 HRSP12 Ribonuclease UK114 1.34 (1.21–1.47) 3.1 × 10−9 No SI, DI Yes
P82980 RBP5 Retinol-binding protein 5 1.30 (1.19–1.42) 1.1 × 10−8 No SI, DI Yes
P14384 CPM Carboxypeptidase M 1.32 (1.20–1.46) 1.9 × 10−8 Yes SI, DI Yes
P55103 INHBC Inhibin β C chain 1.40 (1.25–1.58) 2.3 × 10−8 Yes SI, AIRG, DI Yes
P07327 ADH1A Alcohol dehydrogenase 1A 1.28 (1.17–1.40) 3.0 × 10−8 No SI, AIRG, DI Yes
P04278 SHBG Sex hormone–binding globulin 0.72 (0.64–0.81) 3.5 × 10−8 No SI, AIRG, DI Yes
P10912 GHR Growth hormone receptor 1.40 (1.24–1.58) 6.5 × 10−8 Yes SI, AIRG, DI Yes
Q9BU40 CHRDL1 Chordin-like protein 1 0.69 (0.61–0.79) 7.1 × 10−8 Yes SI, AIRG Yes
P07306 ASGR1 Asialoglycoprotein receptor 1 1.29 (1.17–1.41) 7.4 × 10−8 No SI, DI No
P09467 FBP1 Fructose-1,6-bisphosphatase 1 1.28 (1.17–1.39) 8.9 × 10−8 No SI, AIRG, DI Yes
Q86TH1 ADAMTSL2 ADAMTS-like protein 2 1.30 (1.18–1.43) 1.0 × 10−7 No SI, AIRG, DI Yes
Q8WXD2 SCG3 Secretogranin-3 0.74 (0.66–0.82) 1.1 × 10−7 No SI, AIRG, DI Yes
O94933 SLITRK3 SLIT and NTRK-like protein 3 0.75 (0.67–0.83) 1.2 × 10−7 No SI, AIRG, DI Yes
Q03167 TGFBR3 Transforming growth factor β receptor type 3 0.74 (0.66–0.83) 1.3 × 10−7 No SI, AIRG, DI Yes
P23141 CES1 Liver carboxylesterase 1 1.29 (1.17–1.43) 2.1 × 10−7 No SI, DI No
P00326 ADH1C Alcohol dehydrogenase 1C 1.28 (1.16–1.40) 3.1 × 10−7 No SI, DI No
Q6UXZ4 UNC5D Netrin receptor UNC5D 0.72 (0.63–0.82) 3.1 × 10−7 No SI, AIRG, DI Yes
Q9BZR6 RTN4R Reticulon-4 receptor 1.34 (1.20–1.50) 3.9 × 10−7 Yes SI, DI Yes
Q8N142 ADSSL1 Adenylosuccinate synthetase isozyme 1 1.26 (1.15–1.37) 3.9 × 10−7 No SI, DI Yes
P05062 ALDOB Fructose-bisphosphate aldolase B 1.27 (1.16–1.40) 4.3 × 10−7 No SI, AIRG, DI No
O15335 CHAD Chondroadherin 0.76 (0.68–0.84) 4.6 × 10−7 No SI, DI Yes
O15031 PLXNB2 Plexin-B2 1.36 (1.21–1.54) 6.1 × 10−7 No SI, AIRG No
Q99727 TIMP4 Metalloproteinase inhibitor 4 0.74 (0.66–0.84) 6.2 × 10−7 No AIRG, DI Yes
P04424 ASL Argininosuccinate lyase 1.25 (1.15–1.37) 8.7 × 10−7 No SI, AIRG, DI Yes
O94856 NFASC Neurofascin 1.22 (1.13–1.33) 9.4 × 10−7 No SG No
P08319 ADH4 Alcohol dehydrogenase 4 1.26 (1.15–1.38) 9.9 × 10−7 No SI, AIRG, DI Yes
Q99519 NEU1 Sialidase-1 1.18 (1.11–1.27) 1.1 × 10−6 No SI, DI Yes
Q9NQ79 CRTAC1 Cartilage acidic protein 1 0.77 (0.69–0.86) 1.1 × 10−6 No SI, DI, SG No
Q00796 SORD Sorbitol dehydrogenase 1.29 (1.16–1.42) 1.2 × 10−6 No SI, AIRG, DI No
O95954 FTCD Formimidoyltransferase-cyclodeaminase 1.28 (1.16–1.41) 1.4 × 10−6 No SI, DI Yes
Q6NW40 RGMB RGM domain family member B 0.73 (0.64–0.83) 1.5 × 10−6 No SI, AIRG, DI Yes
Q7Z3B1 NEGR1 § Neuronal growth regulator 1§ 0.74 (0.65–0.84) 1.7 × 10−6 No SI, DI, SG Yes
Q96EE4 CCDC126 Coiled-coil domain-containing protein 126 0.76 (0.68–0.85) 1.7 × 10−6 No SI, AIRG, DI, SG Yes
O00468 AGRN Agrin 1.27 (1.15–1.41) 2.4 × 10−6 No SI, DI No
Q969E1 LEAP2 Liver-expressed antimicrobial peptide 2 1.29 (1.16–1.44) 2.4 × 10−6 No No Yes
Q99972 MYOC Myocilin 0.77 (0.69–0.86) 2.9 × 10−6 No No No
Q13478 IL18R1 Interleukin-18 receptor 1 1.21 (1.12–1.32) 3.6 × 10−6 No SI, DI Yes
Q13332 PTPRS Receptor-type tyrosine-protein phosphatase S 0.78 (0.70–0.87) 3.7 × 10−6 No SI, AIRG, DI Yes
Q01581 HMGCS1 Hydroxymethylglutaryl-CoA synthase, cytoplasmic 1.27 (1.15–1.40) 3.9 × 10−6 No SI Yes
Q9Y617 PSAT1 Phosphoserine aminotransferase 1.25 (1.14–1.37) 4.0 × 10−6 No SI, AIRG, DI Yes
P35442 THBS2 Thrombospondin-2 1.26 (1.14–1.39) 4.5 × 10−6 No AIRG, DI Yes
Q8TF66 LRRC15 Leucine-rich repeat-containing protein 15 0.77 (0.69–0.86) 4.8 × 10−6 No SI, DI No
Q96GG9 DCUN1D1 DCN1-like protein 1 1.22 (1.12–1.34) 9.4 × 10−6 No SI Yes
Q9POT7 TMEM9 Transmembrane protein 9 0.99 (0.88–1.10) 0.40 Yes No No

The model was adjusted for age, sex, race, clinic site, estimated glomerular filtration rate, BMI, smoking status, alcohol consumption status, and education. AIRG, acute insulin response to glucose; DI, Disposition index; HR, hazard ratio; SI: insulin sensitivity; SG: glucose response. HR presents change in risk per SD increase in log2 protein unit at baseline.

*

Also associated with longitudinal glucose in the CHS cohort.

‡

Also associated with at glycemic traits in the HERITAGE cohort.

†

Published proteomic associations with incident type 2 diabetes.

§

Targeted by two distinct aptamers; summary statistics for both are reported in the Supplementary Material.