October 1, 2021Journal of Clinical InvestigationOpen Access

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: COVID-19 (n=13888). Intervention: Chromosome 3 SNP rs10490770 risk allele (C allele) vs. Noncarriers (TT genotype). Primary outcome: All-cause mortality (HR 1.4, 95% CI 1.2-1.7, p=4.5 × 10^-5).

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Key result

Carriers of the chromosome 3 SNP rs10490770 risk allele experienced an increased risk of all-cause mortality (HR 1.4) and severe respiratory failure, with effects more pronounced in individuals 60 years or younger.

Why the study?

There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.

Does carrying the rs10490770 genetic risk allele increase the risk of mortality and severe complications in patients with COVID-19?

Population

13,888 COVID-19 patients (n = 7185 hospitalized) across 17 cohorts in 9 countries

Comparison

rs10490770 risk allele carriers vs non-carriers

Design

Individual-level pooled cohort analysis and meta-analyses

Discussion

Member takes

Overview

May inform risk stratification in younger COVID-19 patients; reinforces chromosome 3 locus as severity modifier.

Study Design

Type

Cohort (n=13,888)

Multicenter

Yes

Structured PICO

Does carrying the rs10490770 genetic risk allele increase the risk of mortality and severe complications in patients with COVID-19?

Population

13,888 patients diagnosed with COVID-19 from 17 cohorts across 9 countries, followed for a median of 43 days to assess the impact of the chromosome 3 genetic risk variant on severity and mortality.

Exposure

Carrier of the chromosome 3 genetic risk variant rs10490770 (C allele, TC or CC genotype)

Comparator

Non-carriers of the rs10490770 genetic risk variant (TT genotype)

Outcome

All-cause mortality and COVID-19-related complications (severe respiratory failure, venous thromboembolism, and hepatic injury) at median 43 days follow-uphard clinical

Main Result

Hazard Ratio: 1.4 (95% CI 1.2–1.7)

p-value: p=4.5 × 10^-5

The chromosome 3 genetic risk variant rs10490770 is a major risk factor for COVID-19 mortality and severe complications, with a significantly stronger impact in patients aged 60 years or younger.

Limitations

Selection bias and ascertainment bias in each cohort
Healthy volunteer bias in the UK Biobank cohort
Low sample size for homozygous carriers preventing meaningful conclusions
Small sample size of non-European ancestry participants
Small sample size in non-European ancestry participants limiting statistical power to investigate ancestry differences
Heterogeneity of the criteria for hospitalization or ICU admission across participating studies
Case-control imbalance in some participating studies

Cite This Study

A 2021 study conducted a cohort in COVID-19 (n=13,888). Chromosome 3 SNP rs10490770 risk allele (C allele) vs. Noncarriers (TT genotype) was evaluated on All-cause mortality (HR 1.4, 95% CI 1.2-1.7, p=4.5 × 10^-5). Carriers of the chromosome 3 SNP rs10490770 risk allele experienced an increased risk of all-cause mortality (HR 1.4) and severe respiratory failure, with effects more pronounced in individuals 60 years or younger.

synapsesocial.com/papers/6a9ac978ba3964d8bb016e8a https://doi.org/10.1172/jci152386

Topics

COVID-19 cardiovascular

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October 1, 2021Journal of Clinical InvestigationOpen Access

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

View Full Paper

Ask AI

Bookmark

Key result

Why the study?

There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.

Does carrying the rs10490770 genetic risk allele increase the risk of mortality and severe complications in patients with COVID-19?

Population

13,888 COVID-19 patients (n = 7185 hospitalized) across 17 cohorts in 9 countries

Comparison

rs10490770 risk allele carriers vs non-carriers

Design

Individual-level pooled cohort analysis and meta-analyses

Discussion

Member takes

Overview

May inform risk stratification in younger COVID-19 patients; reinforces chromosome 3 locus as severity modifier.

Study Design

Type

Cohort (n=13,888)

Multicenter

Yes

Structured PICO

Does carrying the rs10490770 genetic risk allele increase the risk of mortality and severe complications in patients with COVID-19?

Population

13,888 patients diagnosed with COVID-19 from 17 cohorts across 9 countries, followed for a median of 43 days to assess the impact of the chromosome 3 genetic risk variant on severity and mortality.

Exposure

Carrier of the chromosome 3 genetic risk variant rs10490770 (C allele, TC or CC genotype)

Comparator

Non-carriers of the rs10490770 genetic risk variant (TT genotype)

Outcome

All-cause mortality and COVID-19-related complications (severe respiratory failure, venous thromboembolism, and hepatic injury) at median 43 days follow-uphard clinical

Main Result

Hazard Ratio: 1.4 (95% CI 1.2–1.7)

p-value: p=4.5 × 10^-5

The chromosome 3 genetic risk variant rs10490770 is a major risk factor for COVID-19 mortality and severe complications, with a significantly stronger impact in patients aged 60 years or younger.

Limitations

Selection bias and ascertainment bias in each cohort
Healthy volunteer bias in the UK Biobank cohort
Low sample size for homozygous carriers preventing meaningful conclusions
Small sample size of non-European ancestry participants
Small sample size in non-European ancestry participants limiting statistical power to investigate ancestry differences
Heterogeneity of the criteria for hospitalization or ICU admission across participating studies
Case-control imbalance in some participating studies

Cite This Study

synapsesocial.com/papers/6a9ac978ba3964d8bb016e8a https://doi.org/10.1172/jci152386

Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

Topics

COVID-19 cardiovascular

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