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Genetic correlations and causal relationships between cardio-metabolic traits and sepsis

Zhang, Zhongheng ; Chen, Lin ; Zhang, Haoyang LU orcid ; Xiao, Wei ; Yang, Jie ; Huang, Jiajie ; Hu, Qichao ; Jin, Ketao and Hong, Yucai (2024) In Scientific Reports 14. p.1-11
Abstract

Cardio-metabolic traits have been reported to be associated with the development of sepsis. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability, or are confounded by environmental factors. We performed three analyses to explore the relationships between cardio-metabolic traits and sepsis. Mendelian randomization (MR) study to evaluate the causal effects of multiple cardio-metabolic traits on sepsis. Global genetic correlation analysis to explore the correlations between cardio-metabolic traits and sepsis. Local genetic correlation (GC) analysis to explore shared genetic heritability between cardio-metabolic traits and sepsis. Some loci were further examined for related genes... (More)

Cardio-metabolic traits have been reported to be associated with the development of sepsis. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability, or are confounded by environmental factors. We performed three analyses to explore the relationships between cardio-metabolic traits and sepsis. Mendelian randomization (MR) study to evaluate the causal effects of multiple cardio-metabolic traits on sepsis. Global genetic correlation analysis to explore the correlations between cardio-metabolic traits and sepsis. Local genetic correlation (GC) analysis to explore shared genetic heritability between cardio-metabolic traits and sepsis. Some loci were further examined for related genes responsible for the causal relationships. Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies with sample sizes between 200,000 to 750,000. In MR, we found causality between BMI and sepsis (OR: 1.53 [1.4-1.67]; p < 0.001). Body mass index (BMI), which is confirmed by sensitivity analyses and multivariable MR adjusting for confounding factors. Global GC analysis showed a significant correlation between BMI and sepsis (rg = 0.55, p < 0.001). More cardio-metabolic traits were identified to be correlated to the sepsis onset such as CRP (rg = 0.37, p = 0.035), type 2 diabetes (rg = 0.33, p < 0.001), HDL (rg = - 0.41, p < 0.001), and coronary artery disease (rg = 0.43, p < 0.001). Local GC revealed some shared genetic loci responsible for the causality. The top locus 1126 was located at chromosome 7 and comprised genes HIBADH, JAZF1, and CREB5. The present study provides evidence for an independent causal effect of BMI on sepsis. Further detailed analysis of the shared genetic heritability between cardio-metabolic traits and sepsis provides the opportunity to improve the preventive strategies for sepsis.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Humans, Genome-Wide Association Study, Diabetes Mellitus, Type 2/genetics, Causality, Phenotype, Sepsis/genetics, Mendelian Randomization Analysis
in
Scientific Reports
volume
14
article number
5718
pages
1 - 11
publisher
Nature Publishing Group
external identifiers
  • scopus:85186909885
  • pmid:38459230
ISSN
2045-2322
DOI
10.1038/s41598-024-56467-7
language
English
LU publication?
no
additional info
© 2024. The Author(s).
id
7bad413b-137a-4d14-910f-7779770294ab
date added to LUP
2024-03-14 17:14:44
date last changed
2024-04-26 01:06:21
@article{7bad413b-137a-4d14-910f-7779770294ab,
  abstract     = {{<p>Cardio-metabolic traits have been reported to be associated with the development of sepsis. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability, or are confounded by environmental factors. We performed three analyses to explore the relationships between cardio-metabolic traits and sepsis. Mendelian randomization (MR) study to evaluate the causal effects of multiple cardio-metabolic traits on sepsis. Global genetic correlation analysis to explore the correlations between cardio-metabolic traits and sepsis. Local genetic correlation (GC) analysis to explore shared genetic heritability between cardio-metabolic traits and sepsis. Some loci were further examined for related genes responsible for the causal relationships. Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies with sample sizes between 200,000 to 750,000. In MR, we found causality between BMI and sepsis (OR: 1.53 [1.4-1.67]; p &lt; 0.001). Body mass index (BMI), which is confirmed by sensitivity analyses and multivariable MR adjusting for confounding factors. Global GC analysis showed a significant correlation between BMI and sepsis (rg = 0.55, p &lt; 0.001). More cardio-metabolic traits were identified to be correlated to the sepsis onset such as CRP (rg = 0.37, p = 0.035), type 2 diabetes (rg = 0.33, p &lt; 0.001), HDL (rg = - 0.41, p &lt; 0.001), and coronary artery disease (rg = 0.43, p &lt; 0.001). Local GC revealed some shared genetic loci responsible for the causality. The top locus 1126 was located at chromosome 7 and comprised genes HIBADH, JAZF1, and CREB5. The present study provides evidence for an independent causal effect of BMI on sepsis. Further detailed analysis of the shared genetic heritability between cardio-metabolic traits and sepsis provides the opportunity to improve the preventive strategies for sepsis.</p>}},
  author       = {{Zhang, Zhongheng and Chen, Lin and Zhang, Haoyang and Xiao, Wei and Yang, Jie and Huang, Jiajie and Hu, Qichao and Jin, Ketao and Hong, Yucai}},
  issn         = {{2045-2322}},
  keywords     = {{Humans; Genome-Wide Association Study; Diabetes Mellitus, Type 2/genetics; Causality; Phenotype; Sepsis/genetics; Mendelian Randomization Analysis}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{1--11}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Genetic correlations and causal relationships between cardio-metabolic traits and sepsis}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-56467-7}},
  doi          = {{10.1038/s41598-024-56467-7}},
  volume       = {{14}},
  year         = {{2024}},
}