ORCID Profile
0000-0002-5971-2526
Current Organisation
University of Aberdeen
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 06-10-2021
DOI: 10.1101/2020.10.05.20207118
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-s le 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, SLC6A20 and ABO ) had been previously linked with COVID-19 in GWAS. The novel loci included genes involved in interferon pathways ( IL10RB, IFNAR2 and OAS1 ). 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.
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.11.21249617
Abstract: Large genome-wide association studies (GWAS) and other genetic studies have revealed genetic loci that are associated with chronic obstructive pulmonary disease (COPD). However, the proteins responsible for COPD pathogenesis remain elusive. We used integrative-omics by combining genetics of lung function and COPD with genetics of proteome to identify proteins underlying lung function variation and COPD risk. We used summary statistics from the GWAS of human plasma proteome from the INTERVAL cohort (n=3,301) and integrated these data with lung function GWAS results from the UK Biobank cohorts (n=400,102) and COPD GWAS results from the ICGC cohort (35,735 cases and 222,076 controls). We performed in parallel: a proteome-wide Bayesian colocalization, and a proteome-wide Mendelian Randomization (MR) analyses. Next, we selected proteins that colocalized with lung function and/or COPD risk and explored their causal association with lung function and/or COPD using MR analysis ( P 0 . 05 ). We found 537, 607, and 250 proteins that colocalized with force expiratory volume in one second (FEV 1 ), FEV 1 /forced vital capacity (FVC), or COPD risk, respectively. Of these, 1,051 were unique proteins. The sRAGE protein demonstrated the strongest colocalization with FEV 1 /FVC and COPD risk, while QSOX2, FAM3D and F177A proteins had the strongest associations with FEV 1 . Of these, 37 proteins that colocalized with lung function and/or COPD, also had a significant causal association. These included proteins such as PDE4D, QSOX2 and RGAP1, amongst others. Integrative-omics reveals new proteins related to lung function. These proteins may play important roles in the pathogenesis of COPD.
Publisher: European Respiratory Society (ERS)
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
Publisher: European Respiratory Society (ERS)
Date: 24-09-2021
Publisher: Elsevier BV
Date: 10-2021
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ana I Hernandez Cordero.