Table 2.
Significant associations of rs11385942, rs74956615 and rs657152 with plasma proteins among 1671 Black and 7241 white ARIC participants (top 20 for white participants shown for rs657152)
| White participants | Protein | Black participants | Protein | |||||
|---|---|---|---|---|---|---|---|---|
| Variant | Protein | Estimate* (95% CI) | P-value | SD | Estimate* (95% CI) | P-value | SD | |
| rs657152 | ABO system transferase | 2.85 (2.79, 2.92) | <1.0E-300 | 2.71 | 2.13 (1.96, 2.30) | 2.2E-109 | 2.89 | |
| DC-SIGN | 0.33 (0.32, 0.35) | <1.0E-300 | 0.50 | 0.24 (0.21, 0.28) | 2.2E-36 | 0.55 | ||
| Sulfhydryl oxidase 2 | 0.23 (0.22, 0.24) | 1.2E-299 | 0.38 | 0.10 (0.07, 0.12) | 5.0E-15 | 0.36 | ||
| Protein FAM3D | 0.46 (0.44, 0.49) | 9.9E-251 | 0.82 | 0.16 (0.11, 0.21) | 1.4E-10 | 0.74 | ||
| E-selectin | −0.28 (−0.29, −0.26) | 1.9E-223 | 0.52 | −0.14 (−0.18, −0.11) | 9.4E-18 | 0.48 | ||
| D-glucuronyl C5-epimerase | 0.14 (0.13, 0.15) | 2.6E-175 | 0.32 | 0.05 (0.03, 0.07) | 6.6E-06 | 0.32 | ||
| Golgi membrane protein 1 | 0.25 (0.23, 0.27) | 8.1E-144 | 0.45 | 0.09 (0.05, 0.12) | 4.9E-07 | 0.52 | ||
| Golgi membrane protein 1 | 0.19 (0.18, 0.20) | 2.4E-134 | 0.62 | 0.10 (0.06, 0.14) | 1.8E-06 | 0.66 | ||
| Platelet glycoprotein 4 | 0.19 (0.18, 0.21) | 2.4E-109 | 0.53 | 0.17 (0.12, 0.22) | 2.8E-10 | 0.95 | ||
| Protein CASC4 | 0.09 (0.08, 0.10) | 1.1E-86 | 0.26 | 0.04 (0.02, 0.05) | 6.4E-06 | 0.29 | ||
| sTie-1 | 0.09 (0.08, 0.10) | 2.9E-85 | 0.27 | 0.13 (0.11, 0.16) | 3.9E-30 | 0.33 | ||
| Coagulation factor VIII | 0.18 (0.16, 0.19) | 3.8E-81 | 0.54 | 0.16 (0.12, 0.20) | 1.3E-16 | 0.55 | ||
| C1GALT1-specific chaperone 1 | 0.06 (0.06, 0.07) | 3.2E-79 | 0.24 | 0.02 (0.01, 0.03) | 2.4E-03 | 0.20 | ||
| * * Plexin-D1 | −0.09 (−0.10, −0.08) | 3.1E-76 | 0.43 | −0.001 (−0.03, 0.02) | 9.7E-01 | 0.43 | ||
| THSD1 | −0.08 (−0.09, −0.07) | 2.6E-65 | 0.29 | −0.02 (−0.04, −0.001) | 3.5E-02 | 0.27 | ||
| Insulin receptor | −0.11 (−0.12, −0.10) | 2.7E-65 | 0.37 | −0.03 (−0.06, −0.003) | 2.9E-02 | 0.39 | ||
| * * IL-3 receptor subunit alpha | −0.13 (−0.14, −0.11) | 4.4E-63 | 0.47 | 0.02 (−0.008, 0.05) | 1.5E-01 | 0.50 | ||
| P-selectin | −0.10 (−0.11, −0.09) | 5.4E-59 | 0.37 | −0.05 (−0.08, −0.03) | 6.9E-05 | 0.37 | ||
| VEGF receptor 2 | −0.07 (−0.07, −0.06) | 1.7E-56 | 0.24 | −0.02 (−0.04, −0.003) | 1.9E-02 | 0.25 | ||
| LRC-32 | 0.07 (0.06, 0.08) | 2.2E-56 | 0.29 | 0.06 (0.04, 0.08) | 3.9E-09 | 0.32 | ||
| rs74956615 | ICAM-5 | −0.30 (−0.33, −0.27) | 1.4E-77 | 0.42 | −0.31 (−0.49, −0.14) | 5.2E-04 | 0.45 | |
| ICAM-5 | −0.30 (−0.32, −0.26) | 2.2E-70 | 0.43 | −0.30 (−0.48, 0.12) | 8.6E-04 | 0.48 | ||
| ICAM-1 | 0.25 (0.21, 0.29) | 7.3E-34 | 0.53 | 0.18 (0.01, 0.36) | 4.1E-02 | 0.45 | ||
| rs11385942 | * * TDGF-1 | 0.26 (0.19, 0.34) | 6.1E-13 | 1.21 | −0.02 (−0.15, 0.10) | 7.3E-1 | 0.84 | |
| High TDGF-1 | 0.04 (0.00, 0.08) | 2.6E-02 | 0.02 (−0.17, 0.20) | 8.7E-1 | ||||
| Low TDGF-1 | 0.01 (−0.01, 0.03) | 3.3E-01 | 0.01 (−0.04, 0.05) | 8.0E-1 | ||||
Model: General linear regression model adjusted for age, sex, field center, 10 principal components of ancestry and eGFR. Bonferroni correction for multiple testing in white participants, significant associations at P < 1.71E-6. Replication in Black participants for the 84 proteins identified in white participants stipulated a multiple testing corrected threshold of P < 5.95E-4.
*Change in log2 protein associated with one copy increment of at-risk allele for severe COVID-19, e.g. each copy of the rs657152 risk allele was associated with a 2.85 log2 greater ABO system transferase.
* * Variant protein associations that were not replicated in Black participant sample.
ICAM-5 levels were determined by two different DNA aptamers (Supplementary Material, Table S1).
ICAM = intercellular adhesion molecule; DC-SIGN=Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; sTie-1 = Soluble tyrosine-protein kinase receptor Tie-1, THSD1 = Thrombospondin type-1 domain-containing protein; IL = Interleukin; VEGF=Vascular endothelial growth factor; LRC-32 = Leucine-rich repeat-containing protein 32