Table 2.
Glycan/Gene | Discovery cohort (N=1105) | Follow-up study (N=455) | General European population [18] (N=4802) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Glycan | Glycan structure | Locus | Candidate gene | SNP | N | OA, MA (MAF) | R2 | p | β (SE) | p | β (SE) | p |
GP29 | A3G3S3 | 2: 135,014,116 | MGAT5 | rs2460382 | 1044 | A, G (0.21) | 0.04 | 3.14 × 10−11 | 0.01 (0.002) | 2.27 × 10−2 | 0.01 (0.003) | a5.95 × 10−17 |
GP19 | Man9 | 19: 6,713,262 | C3 | rs1047286 | 1033 | G, A (0.20) | 0.04 | 2.43 × 10−11 | −0.03 (0.005) | b8.66 × 10−4 | −0.04 (0.012) | Association not reportedc |
GP19 | Man9 | 19: 6,710,782 | C3 | rs2230203 | 1045 | C, A (0.18) | 0.04 | 4.15 × 10−11 | −0.03 (0.005) | 8.66 × 10−4 | −0.04 (0.012) | Association not reportedc |
GP6 | FA2[6]BG1 | 22: 39,843,409 | MGAT3 | rs5757678 | 1045 | A, G (0.27) | 0.04 | 1.48 × 10−11 | 0.08 (0.012) | 8.63 × 10−7 | 0.11 (0.021) | d7.98 × 10−10 |
GP6 | FA2[6]BG1 | 22: 39,844,793 | MGAT3 | rs5757680 | 1034 | G, A (0.26) | 0.04 | 2.21 × 10−11 | 0.08 (0.012) | 1.35 × 10−6 | 0.10 (0.021) | d7.98 × 10−10 |
Significant associations from the largest GWAS on plasma protein N-glycans comprising 4802 participants from the general European population [18] were searched for the same glycan–SNP association, or SNPs in LD (R2>0.5) with the SNP identified in this study, and the same direction of effect estimates (either increasing or decreasing with the same allele), and their p value is included in this table. Associations identified in this study and not previously reported in the general European population are presented in this table with ‘Association not reported’. Locus information is presented as ‘chromosome number: locus start’. The results are reported for GRCh Build 37, and alleles are aligned to the TOP strand. The β coefficient is reported for the minor allele and expressed as the relative glycan abundance (%)
aResults are reported for rs1257220 (R2=0.98 with rs2460382)
bResults are reported for rs2230203 (R2=0.85 with rs1047286)
cIn the general European population, GP19 was exclusively associated with the chromosome 6 SNP rs3115663 near the PRRC2A gene located in the HLA class III region
dResults are reported for rs909674 (R2=0.91 with rs5757678, R2=0.91 with rs5757680)
N, sample size; OA, other allele; MA, minor allele; MAF, minor allele frequency; R2, percentage of explained glycan variance; F, core fucose α1,6-linked to the inner GlcNAc; Manx, number (x) of mannose residues on core GlcNAcs; Ax, number of antenna (GlcNAc) on the trimannosyl core; A2, biantennary N-glycan; A3, triantennary N-glycan; A2[6], galactose linked on the antenna of the α1,6 mannose; B, bisecting GlcNAc β1,4-linked to β1,4-mannose; Gx, number (x) of linked galactose residues on antenna; Sx, number (x) of sialic acid residues linked to galactose