Ethnic and region-specific genetic risk variants of stroke and its comorbid conditions may better define the variations in the burden of stroke and its phenotypic traits
Curation statements for this article:-
Curated by eLife
eLife assessment
This paper provides a useful analysis of the variation of the burden of strokes across geographic regions, finding differences in the relationship between strokes and their comorbidities. This dataset and the correlations found within will be a resource for directing the focus of future investigations. The statistical analyses are incomplete.
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Abstract
Burden of stroke differs by region, which could be attributed to differences in comorbid conditions and ethnicity. Genomewide variation acts as a proxy marker for ethnicity, and comorbid conditions. We present an integrated approach to understand this variation by considering prevalence and mortality rates of stroke and its comorbid risk for 204 countries from 2009 to 2019, and GWAS risk variant for all these conditions. Global and regional trend analysis of rates using linear regression, correlation and proportion analysis, signify ethnogeographic differences. Interestingly, the comorbid conditions that act as risk drivers for stroke differed by regions, with more of metabolic risk in America and Europe, in contrast to high SBP in Asian and African regions. GWAS risk loci of stroke and its comorbid conditions indicate distinct population stratification for each of these conditions, signifying for population specific risk. Unique and shared genetic risk variants for stroke, and its comorbid and followed up with ethnic specific variation can help in determining regional risk drivers for stroke. Unique ethnic specific risk variants and their distinct patterns of Linkage Disequilibrium further uncover the drivers for phenotypic variation. Therefore, identifying population and comorbidity specific risk variants might help in defining the threshold for risk, and aid in developing population specific prevention strategies for stroke.
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eLife assessment
This paper provides a useful analysis of the variation of the burden of strokes across geographic regions, finding differences in the relationship between strokes and their comorbidities. This dataset and the correlations found within will be a resource for directing the focus of future investigations. The statistical analyses are incomplete.
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Reviewer #1 (Public Review):
Summary:
The paper measures the prevalence and mortality of stroke and its comorbidities across geographic regions in order to find differences in risks that may lead to more effective guidance for these subpopulations. It also does a genetic analysis to look for variants that may drive these phenotypic variations.
Strengths:
The data provided here will provide a foundation for a lot of future research into the causes of the observed correlations as well as whether the observed differences in comorbidities across regions have clinically relevant effects on risk management.
Weaknesses:
As with any cross-national analysis of rates, the data is vulnerable to differences in classification and reporting across jurisdictions. Furthermore, given the increased death rate from COVID-19 associated with many of these …
Reviewer #1 (Public Review):
Summary:
The paper measures the prevalence and mortality of stroke and its comorbidities across geographic regions in order to find differences in risks that may lead to more effective guidance for these subpopulations. It also does a genetic analysis to look for variants that may drive these phenotypic variations.
Strengths:
The data provided here will provide a foundation for a lot of future research into the causes of the observed correlations as well as whether the observed differences in comorbidities across regions have clinically relevant effects on risk management.
Weaknesses:
As with any cross-national analysis of rates, the data is vulnerable to differences in classification and reporting across jurisdictions. Furthermore, given the increased death rate from COVID-19 associated with many of these comorbid conditions and the long-term effects of COVID-19 infection on vascular health, it is expected that many of the correlations observed in this dataset will shift along with the shifting health of the underlying populations.
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Reviewer #2 (Public Review):
Summary:
The authors have analyzed ethnogeographic differences in the comorbidity factors, such as diabetes and heart disease, for the incidences of stroke and whether it leads to mortality.
Strengths:
The idea is interesting and the data are compelling. The results are technically solid.The authors identify specific genetic loci that increase the risk of a stroke and how they differ by region.
Weaknesses:
The presentation is not focused. It would be better to include p-values and focus presentation on the main effects of the dataset analysis.
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