First report on genome wide association study in western Indian population reveals host genetic factors for COVID-19 severity and outcome

Pandit, Ramesh; Singh, Indra; Ansari, Afzal; Raval, Janvi; Patel, Zarna; Dixit, Raghav; Shah, Pranay; Upadhyay, Kamlesh J.; Chuhan, Naresh; Desai, Kairavi; Shah, Meenakshi; Modi, Bhavesh; Joshi, Madhvi; Joshi, Chaitanya

doi:10.1016/j.ygeno.2022.110399

Cited by 4 publications

(4 citation statements)

References 94 publications

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“…We identified the final intergenic variant rs4809972 at locus 20q13.2 , which was 161,552 bp downstream of DOK5 . Another variant near the DOK5 gene, rs60684837, was previously associated with COVID-19 mortality in the western Indian population [ 64 ]. This gene is also associated with obesity [ 65 ] and diabetes, [ 66 ] two comorbidities recurrently identified as COVID-19 risk factors in numerous investigations [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic analysis of severe COVID-19 considering or not asthma comorbidity: GWAS insights from the BQC19 cohort

Amri,

Madore,

Boucher-Lafleur

et al. 2024

BMC Genomics

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Background The severity of COVID-19 is influenced by various factors including the presence of respiratory diseases. Studies have indicated a potential relationship between asthma and COVID-19 severity. Objective This study aimed to conduct a genome-wide association study (GWAS) to identify genetic and clinical variants associated with the severity of COVID-19, both among patients with and without asthma. Methods We analyzed data from 2131 samples sourced from the Biobanque québécoise de la COVID-19 (BQC19), with 1499 samples from patients who tested positive for COVID-19. Among these, 1110 exhibited mild-to-moderate symptoms, 389 had severe symptoms, and 58 had asthma. We conducted a comparative analysis of clinical data from individuals in these three groups and GWAS using a logistic regression model. Phenotypic data analysis resulted in the refined covariates integrated into logistic models for genetic studies. Results Considering a significance threshold of 1 × 10−6, seven genetic variants were associated with severe COVID-19. These variants were located proximal to five genes: sodium voltage-gated channel alpha subunit 1 (SCN10A), desmoplakin (DSP), RP1 axonemal microtubule associated (RP1), IGF like family member 1 (IGFL1), and docking protein 5 (DOK5). The GWAS comparing individuals with severe COVID-19 with asthma to those without asthma revealed four genetic variants in transmembrane protein with EGF like and two follistatin like domains 2 (TMEFF2) and huntingtin interacting protein-1 (HIP1) genes. Conclusion This study provides significant insights into the genetic profiles of patients with severe forms of the disease, whether accompanied by asthma or not. These findings enhance our comprehension of the genetic factors that affect COVID-19 severity. Key messages Seven genetic variants were associated with the severe form of COVID-19; Four genetic variants were associated with the severe form of COVID-19 in individuals with comorbid asthma; These findings help define the genetic component of the severe form of COVID-19 in relation to asthma as a comorbidity.

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Section: Discussionmentioning

confidence: 99%

Genomic analysis of severe COVID-19 considering or not asthma comorbidity: GWAS insights from the BQC19 cohort

Amri,

Madore,

Boucher-Lafleur

et al. 2024

BMC Genomics

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“…Interestingly, TNFSF18, a T-cell receptor that promotes leukocyte adhesion to endothelial cells (51), is enriched in EP6. A SNV found in the proximity of TNFSF18 was found associated with severity of COVID19 in the western Indian population (52). Unfortunately, this SNV was absent from the array used in BQC19 preventing the confirmation of that observation, but it is nevertheless suggestive of a link between TNFSF18, kynurenine, and abnormal coagulation in severe COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Molecular pathology of acute respiratory distress syndrome, mechanical ventilation and abnormal coagulation in severe COVID-19

Soule

William

Liu

et al. 2023

Preprint

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Systemic inflammation in critically ill patients can lead to serious consequences such as acute respiratory distress syndrome (ARDS), a condition characterized by the presence of lung inflammation, edema, and impaired gas exchange, associated with poor survival. Understanding molecular pathobiology is essential to improve critical care of these patients. To this end, we use multimodal profiles of SARS-CoV-2 infected hospitalized participants to the Biobanque Québécoise de la COVID-19 (BQC-19) to characterize endophenotypes associated with different degrees of disease severity. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with endophenotype 6 (EP6). Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. These findings help define the molecular mechanisms related to specific severe outcomes, that can be used to identify early unfavorable clinical trajectories and treatable traits to improve the survival of critically ill patients.

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“…For example, genome-wide significant SNPs identified on chromosome 3 10,11 were not replicated in subsequent studies. 8,12 This inconsistency is probably due to the difference in power (sample size) and population structure. Therefore, combining the results of the COVID-19 GWAS by a metaanalysis can provide accurate results due to an increase in power and effect sizes estimation for specific haplotypes.…”

Section: Coronavirus Disease 2019 (Covid-19) Is a Recently Emerged Vi...mentioning

confidence: 99%

“…Although several genetic variants and loci associated with COVID‐19 have been identified, some of the results from previous GWASs appear to be inconsistent. For example, genome‐wide significant SNPs identified on chromosome 3 10,11 were not replicated in subsequent studies 8,12 . This inconsistency is probably due to the difference in power (sample size) and population structure.…”

Section: Introductionmentioning

confidence: 99%

Host genetic determinants of COVID‐19 susceptibility and severity: A systematic review and meta‐analysis

Eshetie

Jullian

Benyamin

et al. 2023

Reviews in Medical Virology

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Genome‐wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019 (COVID‐19). However, identified SNPs are inconsistent across studies, and there is no compelling consensus that COVID‐19 status is determined by genetic factors. Here, we conducted a systematic review and meta‐analysis to determine the effect of genetic factors on COVID‐19. A random‐effect meta‐analysis was performed to estimate pooled odds ratios (ORs) of SNP effects, and SNP‐based heritability (SNP‐h2) of COVID‐19. The analyses were performed using meta‐R package, and Stata version 17. The meta‐analysis included a total of 96,817 COVID‐19 cases and 6,414,916 negative controls. The meta‐analysis showed that a cluster of highly correlated 9 SNPs (R2 > 0.9) at 3p21.31 gene locus covering LZTFL1 and SLC6A20 genes was significantly associated with COVID‐19 severity, with a pooled OR of 1.8 [1.5–2.0]. Meanwhile, another 3 SNPs (rs2531743‐G, rs2271616‐T, and rs73062389‐A) within the locus was associated with COVID‐19 susceptibility, with pooled estimates of 0.95 [0.93–0.96], 1.23 [1.19–1.27] and 1.15 [1.13–1.17], respectively. Interestingly, SNPs associated with susceptibility and SNPs associated with severity in this locus are in linkage equilibrium (R2 < 0.026). The SNP‐h2 on the liability scale for severity and susceptibility was estimated at 7.6% (Se = 3.2%) and 4.6% (Se = 1.5%), respectively. Genetic factors contribute to COVID‐19 susceptibility and severity. In the 3p21.31 locus, SNPs that are associated with susceptibility are not in linkage disequilibrium (LD) with SNPs that are associated with severity, indicating within‐locus heterogeneity.

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First report on genome wide association study in western Indian population reveals host genetic factors for COVID-19 severity and outcome

Cited by 4 publications

References 94 publications

Genomic analysis of severe COVID-19 considering or not asthma comorbidity: GWAS insights from the BQC19 cohort

Genomic analysis of severe COVID-19 considering or not asthma comorbidity: GWAS insights from the BQC19 cohort

Molecular pathology of acute respiratory distress syndrome, mechanical ventilation and abnormal coagulation in severe COVID-19

Host genetic determinants of COVID‐19 susceptibility and severity: A systematic review and meta‐analysis

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