Genetic Risk Prediction of COVID-19 Susceptibility and Severity in the Indian Population

  1. P. Prakrithi
  2. Priya Lakra
  3. Durai Sundar
  4. Manav Kapoor
  5. Mitali Mukerji
  6. Ishaan Gupta
  7. The Indian Genome Variation Consortium

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Abstract

Host genetic variants can determine their susceptibility to COVID-19 infection and severity as noted in a recent Genome-wide Association Study (GWAS). Given the prominent genetic differences in Indian sub-populations as well as differential prevalence of COVID-19, here, we compute genetic risk scores in diverse Indian sub-populations that may predict differences in the severity of COVID-19 outcomes. We utilized the top 100 most significantly associated single-nucleotide polymorphisms (SNPs) from a GWAS by Pairo-Castineira et al . determining the genetic susceptibility to severe COVID-19 infection, to compute population-wise polygenic risk scores (PRS) for populations represented in the Indian Genome Variation Consortium (IGVC) database. Using a generalized linear model accounting for confounding variables, we found that median PRS was significantly associated ( p < 2 x 10 −16 ) with COVID-19 mortality in each district corresponding to the population studied and had the largest effect on mortality (regression coefficient = 10.25). As a control we repeated our analysis on randomly selected 100 non-associated SNPs several times and did not find significant association. Therefore, we conclude that genetic susceptibility may play a major role in determining the differences in COVID-19 outcomes and mortality across the Indian sub-continent. We suggest that combining PRS with other observed risk-factors in a Bayesian framework may provide a better prediction model for ascertaining high COVID-19 risk groups and to design more effective public health resource allocation and vaccine distribution schemes.

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  1. Version published to 10.3389/fgene.2021.714185
  2. Version published to 10.1101/2021.04.13.21255447v2 on medRxiv
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    SciScore for 10.1101/2021.04.13.21255447: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

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    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are certain limitations of the present study. The GWAS study was not directly conducted in the individuals of the Indian sub-populations, and the PRSs were based on effect sizes from different ancestral groups with COVID-19 infection. The mortality may also be affected by comorbidities like age, diabetes, hypertension, cardiovascular diseases16–18 and environmental risk factors that can act as confounders. Further, the current study does not model the effect of confounders such as population density that could also affect the COVID-19 spread and mortality. Smaller populations might have less exposure to the virus, and therefore can display low mortality despite carrying a high PRS. For instance, IEELP4 population (Kandhamal district, population size and density of 7.3 lakhs and 90/km2 respectively) has a high PRS but the number of deaths in this district is low, compared to other larger populations (with population size of 10-40 lakhs) with high PRS. Moreover, considering the districts having a similar population size and density (i.e. by removing the outliers), the correlation improved, although not significantly (R=0.43, p=0.092), suggesting that population density could act as a confounding factor. Also, a similar trend was observed in the number of cases over several months in the populations, suggesting that there could be a genetic basis for this trend (Supplementary Fig. S3). The prediction accuracy can be improved by using sequencing data and since IGVC is array...

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    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
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  4. Version published to 10.1101/2021.04.13.21255447v1 on medRxiv