Combining Mendelian Randomization and Experimental Approaches for the Identification of miRNAs related to Major Depressive Diso
(2024) BINP52 20232Degree Projects in Bioinformatics
- Abstract
- Major depressive disorder (MDD) is a prevalent psychiatric condition and poses a significant burden on public health. The underlying causes and mechanisms of depression remain poorly understood. There is a growing body of evidence linking microRNAs (miRNAs) to major depressive disorder (MDD). However, the causal relationship between miRNAs and MDD remains unclear. This study aimed to investigate the potential causal association between miRNAs and MDD by combining Mendelian Randomization (MR) analyses and experimental approaches.
Single nucleotide polymorphisms (SNPs) significantly associated with the expression levels of miRNAs identified in the Framingham Heart Study (FHS) were used as the instrument variables being a proxy for miRNA... (More) - Major depressive disorder (MDD) is a prevalent psychiatric condition and poses a significant burden on public health. The underlying causes and mechanisms of depression remain poorly understood. There is a growing body of evidence linking microRNAs (miRNAs) to major depressive disorder (MDD). However, the causal relationship between miRNAs and MDD remains unclear. This study aimed to investigate the potential causal association between miRNAs and MDD by combining Mendelian Randomization (MR) analyses and experimental approaches.
Single nucleotide polymorphisms (SNPs) significantly associated with the expression levels of miRNAs identified in the Framingham Heart Study (FHS) were used as the instrument variables being a proxy for miRNA exposure. The outcome was derived from the genome-wide association study (GWAS) of MDD (cases=170,756, controls=329,443). Two-sample MR was conducted to assess the association of miRNAs with MDD. The miRNAs identified from MR analyses were further validated in blood samples from individuals in the Women's Health in Lund Area (WHILA) cohort using qPCR.
The MR analysis revealed that six miRNAs were significantly associated with MDD, which included miR-133a-3p [Odds Ratio (OR)=1.03, 95% Confidence interval (CI):1.00-1.05], miR-130a-3p (OR=1.06, 95% CI:1.03-1.09), miR-138-5p (OR=1.06, 95% CI:1.01-1.11), miR-629-5p (OR=0.96, 95% CI:0.93-0.99), miR-132-3p (OR=0.97, 95% CI:0.94-1.00) and miR-635-3p (OR=0.97, 95% CI:0.95-0.99). Among them, miR-130a-3p (OR=2.06, 95% CI:1.08-4.28, P=0.04) and miR-132-3p (OR=0.51, 95% CI:0.29-0.88, P=0.02) were further confirmed to be associated with MDD following experimental approaches.
In conclusion, the results from MR analyses and experimental studies provide further evidence supporting a potential causal association between certain miRNAs and MDD. (Less) - Popular Abstract
- Major depressive disorder (MDD) is a common mental disorder caused the feelings of anxiety and sadness. People with MDD find it difficult to concentrate on their works, lose interest in activities they once enjoyed, and may even contemplate or attempt suicide. Unlike typical mood swings, MDD arises from a complex interplay of genetic and environmental factors. Despite extensive research, the exact mechanisms behind MDD remain elusive.
Recently, scientists have been paying more attention to epigenetics, especially the role of microRNAs (miRNAs). These small molecules regulate gene expression without changing the sequence of DNA. They can inhibit or degrade target mRNA, leading to reduced gene activity and protein production. Notably,... (More) - Major depressive disorder (MDD) is a common mental disorder caused the feelings of anxiety and sadness. People with MDD find it difficult to concentrate on their works, lose interest in activities they once enjoyed, and may even contemplate or attempt suicide. Unlike typical mood swings, MDD arises from a complex interplay of genetic and environmental factors. Despite extensive research, the exact mechanisms behind MDD remain elusive.
Recently, scientists have been paying more attention to epigenetics, especially the role of microRNAs (miRNAs). These small molecules regulate gene expression without changing the sequence of DNA. They can inhibit or degrade target mRNA, leading to reduced gene activity and protein production. Notably, circulating miRNAs found in body fluids like plasma show promise as biomarkers for diagnosing MDD and evaluating treatment responses. Observational studies have indicated that people with MDD often exhibit significantly different levels of certain circulating miRNAs compared to those without this disorder. However, it is still unclear whether these miRNAs changes are a cause or a consequence of MDD.
To explore this relationship, our study employed Mendelian Randomization (MR), a method that helps determine whether a particular risk factor (in this case, miRNAs) can lead to an outcome (MDD) using genetic data. MR mimics the randomized controlled trials (RCTs), which are the gold standard to identify causal relationships. By leveraging the random inheritance of genetic variants, we aimed to see if individuals with variants impacting miRNA expression were more likely to experience MDD.
In our study, we identified six identified miRNAs using MR analysis and validated them through a nested case-control study involving 104 (52 cases, 52 controls) blood samples from the Women's Health in Lund Area (WHILA) cohort. Our findings revealed that miR-130a-3p and miR-132-3p have potential causal relationship with MDD, supported by both MR and experimental validation. This result not only enhances our understanding of the mechanism of MDD, but also suggests that these miRNAs may serve as potential biomarkers for MDD. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9175552
- author
- Cao, Linlin
- supervisor
-
- Xiao Wang LU
- organization
- course
- BINP52 20232
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9175552
- date added to LUP
- 2024-09-27 11:07:33
- date last changed
- 2024-09-27 11:07:33
@misc{9175552,
abstract = {{Major depressive disorder (MDD) is a prevalent psychiatric condition and poses a significant burden on public health. The underlying causes and mechanisms of depression remain poorly understood. There is a growing body of evidence linking microRNAs (miRNAs) to major depressive disorder (MDD). However, the causal relationship between miRNAs and MDD remains unclear. This study aimed to investigate the potential causal association between miRNAs and MDD by combining Mendelian Randomization (MR) analyses and experimental approaches.
Single nucleotide polymorphisms (SNPs) significantly associated with the expression levels of miRNAs identified in the Framingham Heart Study (FHS) were used as the instrument variables being a proxy for miRNA exposure. The outcome was derived from the genome-wide association study (GWAS) of MDD (cases=170,756, controls=329,443). Two-sample MR was conducted to assess the association of miRNAs with MDD. The miRNAs identified from MR analyses were further validated in blood samples from individuals in the Women's Health in Lund Area (WHILA) cohort using qPCR.
The MR analysis revealed that six miRNAs were significantly associated with MDD, which included miR-133a-3p [Odds Ratio (OR)=1.03, 95% Confidence interval (CI):1.00-1.05], miR-130a-3p (OR=1.06, 95% CI:1.03-1.09), miR-138-5p (OR=1.06, 95% CI:1.01-1.11), miR-629-5p (OR=0.96, 95% CI:0.93-0.99), miR-132-3p (OR=0.97, 95% CI:0.94-1.00) and miR-635-3p (OR=0.97, 95% CI:0.95-0.99). Among them, miR-130a-3p (OR=2.06, 95% CI:1.08-4.28, P=0.04) and miR-132-3p (OR=0.51, 95% CI:0.29-0.88, P=0.02) were further confirmed to be associated with MDD following experimental approaches.
In conclusion, the results from MR analyses and experimental studies provide further evidence supporting a potential causal association between certain miRNAs and MDD.}},
author = {{Cao, Linlin}},
language = {{eng}},
note = {{Student Paper}},
title = {{Combining Mendelian Randomization and Experimental Approaches for the Identification of miRNAs related to Major Depressive Diso}},
year = {{2024}},
}