Table 3.

Multi-omics associations with CpG methylation in QMDiab

Locus	Group	Trait	Trend	P-Value
UGT2B15 cg09189601 chr4: 69514031 Other	Metabolites	X-19141 [plasma]	↓	6.21 ×10−23
TXNIP cg19693031 chr1: 145441552 Diabetes	Metabolites	1, 5-anhydroglucitol (1, 5-AG) [plasma]a	↑	7.56 × 10−21
		Glucose [NMR]	↓	1.17 × 10−14
		2-hydroxybutyrate (AHB) [urine]	↓	2.52 × 10−14
		3-hydroxybutyrate (BHBA) [urine]	↓	5.87 × 10−13
		glucose [plasma]a	↓	3.15 × 10−12
		… (list truncated)
	Lipids	L-VLDL-CE_%	↑	1.01 × 10−8
		XL-VLDL-CE_%	↑	2.05 × 10−8
		M-VLDL-CE_%	↑	4.42 × 10−6
		XL-VLDL-C_%	↑	5.66 × 10−6
		… (list truncated)
	Proteins	Transmembrane glycoprotein NMB (GPNMB)	↓	1.30 × 10−8
		Aminoacylase-1 (ACY1)	↓	2.59 × 10−7
		Sex hormone-binding globulin (SHBG)	↑	4.65 × 10−7
		Melanoma-derived growth regulatory protein (MIA)	↑	6.88 × 10−7
	Glycans	PGP23	↓	2.75 × 10−8
		PGP31	↓	9.31 × 10−8
		PGP29	↓	7.61 × 10−6
		PGP28	↓	8.42 × 10−6
DHCR24 cg17901584 chr1: 55353706 Obesity	Lipids	M-VLDL-C_%	↑	6.62 × 10−9
		M-VLDL-TG_%	↓	7.14 × 10−9
		M-VLDL-CE_%	↑	1.87 × 10−8
		S-VLDL-TG_%	↓	1.36 × 10−6
		… (list truncated)
MYO5C cg06192883 chr15: 52554171 Obesity	Glycans	PGP58	↑	8.31 × 10−9
		PGP70	↑	6.91 × 10−8
		PGP1	↑	3.67 × 10−7
		PGP17	↓	8.34 × 10−7
		PGP99	↑	1.23 × 10−6
		… (list truncated)
		IgG1_G0F	↑	9.46 × 10−7
		IgG4_G2FN	↓	1.79 × 10−5
ABCG1 cg06500161 chr21: 43656587 Diabetes and obesity	Metabolites	Myo-inositol [urine]	↑	7.21 × 10−7
	Lipids	L-VLDL-CE_%	↓	1.03 × 10−8
		M-VLDL-CE_%	↓	2.19 × 10−7
		M-VLDL-C_%	↓	2.26 × 10−7
		XXL-VLDL-CE_%	↓	8.73 × 10−7
		… (list truncated)
CPT1A cg00574958 chr11: 68607622 Diabetes and obesity	Proteins	Tumor necrosis factor ligand superfamily member 4 (TNFSF4)	↑	1.61 × 10−6
SLC7A11 cg06690548 chr4: 139162808 Obesity	Metabolites	Serine [plasma]	↑	3.05 × 10−7
AHRR cg05575921 chr5: 373378 Smoking	Metabolites	o-cresol sulfate [urine]	↓	2.66 × 10−27
		3-ethylphenylsulfate* [urine]	↓	1.08 × 10−17
		X-17185 [urine]b X-17185 [plasma]	↓ ↓	2.42 × 10−16, 1.52 × 10−7
		X-12161 [urine]	↓	5.17 × 10−13
		X-17398 [urine]	↓	1.36 × 10−12
		… (list truncated)
	Proteins	Polymeric immunoglobulin receptor (PIGR)	↓	2.03 × 10−11
ALPPL2 cg21566642 chr2: 233284661 Smoking	Metabolites	o-Cresol sulfate [urine]	↓	7.43 × 10−16
		3-ethylphenylsulfate* [urine]	↓	4.45 × 10−9
		X-17185 [plasma]b X-17185 [urine]	↓ ↓	6.32 × 10−8, 1.15 × 10−6
		X-17398 [urine]	↓	6.35 × 10−8
		2-ethylphenylsulfate [urine]	↓	4.54 × 10−7
F2RL3 cg03636183 chr19: 17000585 Smoking	Metabolites	o-Cresol sulfate [urine]	↓	4.93 × 10−13
		3-ethylphenylsulfate* [urine]	↓	1.09 × 10−9
		X-17398 [urine]	↓	1.41 × 10−8
		X-17185 [urine]	↓	9.18 × 10−7
	Proteins	Polymeric immunoglobulin receptor (PIGR)	↓	9.02 × 10−7
cg06126421 chr6: 30720080 Smoking	Metabolites	X-17185 [urine]b X-17185 [plasma]	↓ ↓	2.99 × 10−10, 6.23 × 10−7
		o-Cresol sulfate [urine]	↓	2.23 × 10−9
		X-17398 [urine]	↓	2.49 × 10−7
		3-ethylphenylsulfate* [urine]	↓	5.37 × 10−7
		X-17320 [urine]	↓	5.47 × 10−7
		3-methyl catechol sulfate 1 [urine]	↓	5.53 × 10−7
	Proteins	Polymeric immunoglobulin receptor (PIGR)	↓	3.36 × 10−7
RARA cg19572487 chr17: 38476024 Smoking	Metabolites	o-Cresol sulfate [urine]	↓	3.29 × 10−7
	Proteins	Gelsolin (GSN)	↑	1.89 × 10−6
GFI1 cg09935388 chr1: 92947588 Smoking	Metabolites	o-Cresol sulfate [urine]	↓	2.90 × 10−7
cg23079012 chr2: 8343710 Smoking	Metabolites	o-Cresol sulfate [urine]	↓	4.51 × 10−8
	Proteins	X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2)	↓	4.35 × 10−9
		Vascular endothelial growth factor A (VEGFA)	↓	1.42 × 10−6
		NudC domain-containing protein 3 (NUDCD3)	↓	1.55 × 10−6

Association data for 14 of the 20 CpG loci reported by Petersen et al. (25). P-values are for the reported phenotypes in linear regression models with the respective covariates (Fig. 2). Associations were required to reach a Bonferroni level of significance of p_metabolite < 1.01 × 10⁻⁶, p_lipid < 1.11 × 10⁻⁵, p_protein < 2.22 × 10⁻⁶, and p_glycan < 2.21 × 10⁻⁵ for metabolites, lipids, proteins, and glycan traits, respectively. Genomic coordinates are based on human genome build 37. A positive association with methylation levels is indicated by (↑), while a negative is indicated by (↓). Full summary statistics are in Supplementary Material, Table S3.

^aThis metabolite was already reported in Petersen et al.

^bThis metabolite was measured on different platforms or in different fluids in QMDiab (indicated in square brackets).

Note: We only present the five most significant associations for each category in this table. For a more comprehensive list, see Supplementary Material, Table S3.