Analysis of susceptibility genes and myocardial infarction risk correlation of ischemic cardiomyopathy based on bioinformatics

Background The present study was to investigated differential expressed genes (GEGs) in ischemic cardiomyopathy (ICM), and to construct regulation networks, and to study the correlation between myocardial infarction risk. Methods Data sets were downloaded from the Gene Expression Omnibus (GEO) to screen out messenger RNA (mRNA) and long non-coding RNA (lncRNA) differentially expressed between ICM samples and normal samples. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Differentially expressed mRNA and lncRNA were analyzed, and bioinformatics methods were used to predict and analyze microRNA (miRNA), and a competing endogenous RNA (Hub gene) regulatory network was constructed. Using the Limma software package in R language, DEGs of ICM were screened with non-heart failure donors as the control group under the conditions that the differential expression ratio was not less than 2 times, and the corrected P value was <0.05. The ClusterProfiler software package was used for GO enrichment analysis and KEGG enrichment analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.0 online database was used to screen key genes for protein-protein interaction (PPI) network analysis. Results The GO function analysis and KEGG pathway analysis showed that the DEGs were significantly enriched in metabolic pathways, oxidative phosphorylation, extracellular matrix receptor interactions, and other pathways, and were closely related to fibrosis, collagen catabolic process, and inflammatory response function, and a Hub gene regulatory network related to ICM lncRNA was constructed. Bioinformatics methods were used to effectively analyze the DEGs of ICM, and the Hub gene regulatory network of ICM was successfully constructed. Conclusions This study identified a certain risk correlation between ICM susceptibility genes and myocardial infarction.


Introduction
Background rationale 2 Explain the scientific background and rationale for the investigation being reported.
Objectives 3 State specific objectives, including any pre-specified hypotheses.
(State if the study is the first report of a genetic association, a replication effort, or both.)

Study design 4
Present key elements of study design early in the paper.
Setting 5 Describe the setting, locations and relevant dates, including periods of recruitment, exposure, follow-up, and data collection.
Participants 6 (a) Cohort study -Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up.
Case-control study -Give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls. Cross-sectional study -Give the eligibility criteria, and the sources and methods of selection of participants.
(Give information on the criteria and methods for selection of subsets of participants from a larger study, when relevant.) (b) Cohort study -For matched studies, give matching criteria and number of exposed and unexposed. Case-control study -For matched studies, give matching criteria and the number of controls per case.
Variables 7 (a) Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable. (b) Clearly define genetic exposures (genetic variants) using a widely-used nomenclature system. Identify variables likely to be associated with population stratification (confounding by ethnic origin).

STREGA Reporting Recommendations, Extended from STROBE Statement
Data sources/ measurement 8* (a) For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group. (b) Describe laboratory methods, including source and storage of DNA, genotyping methods and platforms (including the allele calling algorithm used, and its version), error rates and call rates. State the laboratory/centre where genotyping was done. Describe comparability of laboratory methods if there is more than one group. Specify whether genotypes were assigned using all of the data from the study simultaneously or in smaller batches.
Bias 9 (a) Describe any efforts to address potential sources of bias.
(b) or quantitative outcome variables, specify if any investigation of potential bias resulting from pharmacotherapy was undertaken. If relevant, describe the nature and magnitude of the potential bias, and explain what approach was used to deal with this.
Study size 10 Explain how the study size was arrived at.

Quantitative variables 11
Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen, and why.
(If applicable, describe how effects of treatment were dealt with.) Statistical methods

12
(a) Describe all statistical methods, including those used to control for confounding.
[State software version used and options (or settings) chosen.] (b) Describe any methods used to examine subgroups and interactions.
(c) Explain how missing data were addressed.
(d) Cohort study -If applicable, explain how loss to follow-up was addressed.
Case-control study -If applicable, explain how matching of cases and controls was addressed.
Cross-sectional study -If applicable, describe analytical methods taking account of sampling strategy.
(e) Describe any sensitivity analyses.
(f) State whether Hardy-Weinberg equilibrium was considered and, if so, how.
(g) Describe any methods used for inferring genotypes or haplotypes.
(h) Describe any methods used to assess or address population stratification.
(i) Describe any methods used to address multiple comparisons or to control risk of false positive findings.
(j) Describe any methods used to address and correct for relatedness among subjects

Results
Participants 13* (a) Report the numbers of individuals at each stage of the study -e.g., numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed.
(Report numbers of individuals in whom genotyping was attempted and numbers of individuals in whom genotyping was successful).
(b) Give reasons for non-participation at each stage.
(c) Consider use of a flow diagram.
Descriptive data 14* (a) Give characteristics of study participants (e.g., demographic, clinical, social) and information on exposures and potential confounders. (c) Cohort study -Summarize follow-up time (e.g., average and total amount).
Outcome data 15* Cohort study -Report numbers of outcome events or summary measures over time.
[Report outcomes (phenotypes) for each genotype category over time] Case-control study -Report numbers in each exposure category, or summary measures of exposure.

(Report numbers in each genotype category)
Cross-sectional study -Report numbers of outcome events or summary measures.
[Report outcomes (phenotypes) for each genotype category] Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (e.g., 95% confidence intervals). Make clear which confounders were adjusted for and why they were included.
(b) Report category boundaries when continuous variables were categorized.
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period.
(d) Report results of any adjustments for multiple comparisons.
Other analyses 17 (a) Report other analyses done -e.g., analyses of subgroups and interactions, and sensitivity analyses.
(b) If numerous genetic exposures (genetic variants) were examined, summarize results from all analyses undertaken.
(c) If detailed results are available elsewhere, state how they can be accessed.

Discussion
Key results 18 Summarize key results with reference to study objectives.

Limitations 19
Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias.
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence.

Generalizability 21
Discuss the generalizability (external validity) of the study results.

Other Information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based.