Your browser doesn't support javascript.
Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study.
Steffen, Brian T; Pankow, James S; Lutsey, Pamela L; Demmer, Ryan T; Misialek, Jeffrey R; Guan, Weihua; Cowan, Logan T; Coresh, Josef; Norby, Faye L; Tang, Weihong.
  • Steffen BT; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Pankow JS; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lutsey PL; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Demmer RT; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Misialek JR; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
  • Guan W; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
  • Cowan LT; Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA.
  • Coresh J; Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Jiann Ping-Hsu College of Public Health, Statesboro, GA 30458, USA.
  • Norby FL; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
  • Tang W; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
Hum Mol Genet ; 31(14): 2452-2461, 2022 07 21.
Article in English | MEDLINE | ID: covidwho-1713662
ABSTRACT

BACKGROUND:

Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes.

METHODS:

A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up.

RESULTS:

The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR) 0.87; P = 2.3 × 10-11) and von Willebrand factor type A (HR 1.17; P = 1.6x10-13).

CONCLUSIONS:

Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Genetic Predisposition to Disease / COVID-19 Type of study: Cohort study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Hum Mol Genet Journal subject: Molecular Biology / Genetics, Medical Year: 2022 Document Type: Article Affiliation country: Hmg

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Genetic Predisposition to Disease / COVID-19 Type of study: Cohort study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Hum Mol Genet Journal subject: Molecular Biology / Genetics, Medical Year: 2022 Document Type: Article Affiliation country: Hmg