Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19
Abstract SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We therefore used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian randomization to combine gene expression quantitative trait loci (eQTLs) from the Lung eQTL (n=1,038) and eQTLGen (n=31,784) studies with published COVID-19 genome-wide association study (GWAS) data from the COVID-19 Host Genetics Initiative. Additionally, we used COLOC to integrate plasma protein quantitative trait loci (pQTL) from the INTERVAL study (n=3,301) with COVID-19-associated loci. Finally, we determined any causal associations between plasma proteins and COVID-19 using multi-variable two-sample Mendelian randomization (MR). We found that the expression of 20 genes in lung and 31 genes in blood was associated with COVID-19. Of these genes, only three (LZTFL1, SLC6A20andABO) had been previously linked with COVID-19 in GWAS. The novel loci included genes involved in interferon pathways (IL10RB, IFNAR2andOAS1). Plasma ABO protein, which is associated with blood type in humans, demonstrated a significant causal relationship with COVID-19 in MR analysis; increased plasma levels were associated with an increased risk of having COVID-19 and risk of severe COVID-19. In summary, our study identified genes associated with COVID-19 that may be prioritized for future investigation. Importantly, this is the first study to demonstrate a causal association between plasma ABO protein and COVID-19..
Medienart: |
Preprint |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 09. Okt. Zur Gesamtaufnahme - year:2023 |
---|
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Hernández Cordero, Ana I. [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Themen: |
---|
doi: |
10.1101/2020.10.05.20207118 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
XBI019078439 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | XBI019078439 | ||
003 | DE-627 | ||
005 | 20231205150441.0 | ||
007 | cr uuu---uuuuu | ||
008 | 201010s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/2020.10.05.20207118 |2 doi | |
035 | |a (DE-627)XBI019078439 | ||
035 | |a (biorXiv)10.1101/2020.10.05.20207118 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Hernández Cordero, Ana I. |e verfasserin |0 (orcid)0000-0002-5971-2526 |4 aut | |
245 | 1 | 0 | |a Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19 |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Abstract SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We therefore used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian randomization to combine gene expression quantitative trait loci (eQTLs) from the Lung eQTL (n=1,038) and eQTLGen (n=31,784) studies with published COVID-19 genome-wide association study (GWAS) data from the COVID-19 Host Genetics Initiative. Additionally, we used COLOC to integrate plasma protein quantitative trait loci (pQTL) from the INTERVAL study (n=3,301) with COVID-19-associated loci. Finally, we determined any causal associations between plasma proteins and COVID-19 using multi-variable two-sample Mendelian randomization (MR). We found that the expression of 20 genes in lung and 31 genes in blood was associated with COVID-19. Of these genes, only three (LZTFL1, SLC6A20andABO) had been previously linked with COVID-19 in GWAS. The novel loci included genes involved in interferon pathways (IL10RB, IFNAR2andOAS1). Plasma ABO protein, which is associated with blood type in humans, demonstrated a significant causal relationship with COVID-19 in MR analysis; increased plasma levels were associated with an increased risk of having COVID-19 and risk of severe COVID-19. In summary, our study identified genes associated with COVID-19 that may be prioritized for future investigation. Importantly, this is the first study to demonstrate a causal association between plasma ABO protein and COVID-19. | ||
650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
700 | 1 | |a Li, Xuan |4 aut | |
700 | 1 | |a Milne, Stephen |0 (orcid)0000-0001-5274-1298 |4 aut | |
700 | 1 | |a Yang, Chen Xi |4 aut | |
700 | 1 | |a Bossé, Yohan |4 aut | |
700 | 1 | |a Joubert, Philippe |4 aut | |
700 | 1 | |a Timens, Wim |4 aut | |
700 | 1 | |a van den Berge, Maarten |4 aut | |
700 | 1 | |a Nickle, David |4 aut | |
700 | 1 | |a Hao, Ke |4 aut | |
700 | 1 | |a Sin, Don D. |4 aut | |
773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 09. Okt. |
773 | 1 | 8 | |g year:2023 |g day:09 |g month:10 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.10.05.20207118 |z kostenfrei |3 Volltext |
912 | |a GBV_XBI | ||
951 | |a AR | ||
952 | |j 2023 |b 09 |c 10 |