The challenge of Mendelian randomization approach

Zoccali, Carmine

doi:10.1080/03007995.2017.1378514

Cited by 8 publications

(4 citation statements)

References 15 publications

(17 reference statements)

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“…Mendelian randomization (MR) is an emerging method of epidemiological analysis that uses genetic variation as a tool to assess causal relationships between exposures and clinical outcomes ( 12 , 13 ). The method is founded on the principle of random distribution in biology, which makes its results immune to potential confounders and reverse causation.…”

Section: Introductionmentioning

confidence: 99%

The immune factors have complex causal regulation effects on inflammatory bowel disease

Qiu,

Zhang,

Qin

et al. 2024

Front. Immunol.

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BackgroundAlthough a correlation between immune cell phenotypes and inflammatory bowel disease (IBD) has been established, a causal relationship remains unestablished.MethodsTo assess causal associations between immune cell phenotypes and IBD and its subtypes, we employed Mendelian randomization (MR) methods and genome-wide association studies (GWAS) summary statistics. The primary outcomes were determined based on the inverse variance weighting (IVW) results, with the assessment of heterogeneity and pleiotropy conducted through Cochrane’s Q-test and MR-Egger. The stability of the MR results was then examined using leave-one-out analysis, and false discovery rate (FDR) correction was applied to evaluate the strength of the causal relationship between exposure and outcome. Furthermore, to identify immunophenotypes strongly associated with IBD, a meta-integration of the effect values of all positive results in both datasets was conducted.ResultsThe analysis of 731 immune cell phenotypes and IBD using MR techniques revealed potential causal associations between 26 phenotypes and IBD. Subsequent meta-integration of the two datasets provided evidence of solid causal associations between 20 immune phenotypes and IBD and its subtypes. Nominal causal associations were also identified in the remaining six immune phenotypes and IBD and its subtypes.ConclusionOur study confirms causal solid associations between 20 immune phenotypes and IBD, thus guiding future clinical studies.

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Section: Introductionmentioning

confidence: 99%

The immune factors have complex causal regulation effects on inflammatory bowel disease

Qiu,

Zhang,

Qin

et al. 2024

Front. Immunol.

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“…This study used inverse variance-weighted [IVW] meta-analysis to investigate and assess the causal relationships between exposure, intermediate, and outcome ( 26 ). The IVW method is the primary MR analysis method used for combining the Wald ratios of individual SNPs ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

Application and discoveries of metabolomics and proteomics in the study of female infertility

Shi,

Wu,

et al. 2024

Front. Endocrinol.

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IntroductionFemale infertility is defined as the absence of clinical pregnancy after 12 months of regular unprotected sexual intercourse.MethodsThis study employed metabolomics and proteomics approaches to investigate the relationship between metabolites and proteins and female infertility. The study used metabolomics and proteomics data from the UK Biobank to identify metabolites and proteins linked to infertility.ResultsThe results showed that GRAM domain-containing protein 1C and metabolites fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and 3-Hydroxybutyrate had a positive correlation with infertility, whereas proteins such as Interleukin-3 receptor subunit alpha, Thrombospondin type-1 domain-containing protein 1, Intestinal-type alkaline phosphatase, and platelet and endothelial cell adhesion molecule 1 exhibited a negative correlation. These findings provide new clues and targets for infertility diagnosis and treatment. However, further research is required to validate these results and gain a deeper understanding of the specific roles of these metabolites and proteins in infertility pathogenesis.DiscussionIn conclusion, metabolomics and proteomics techniques have significant application value in the study of infertility, allowing for a better understanding of the biological mechanisms underlying infertility and providing new insights and strategies for its diagnosis and treatment. These research findings provide a crucial biological mechanistic basis for early infertility screening, prevention, and treatment.

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“…Additionally, Porphyromonas gingivalis and Porphyromonas solanacearum were found to induce butyrate-associated cellular senescence, promoting CRC (Okumura et al, 2021). Although randomized controlled trials are the gold standard for studying causality, they are difficult to implement and design due to constraints such as ethics, subject compliance, and study duration (Zoccali, 2017;. To address this issue, a new method called Mendelian randomization (MR) utilizes genetic tools to assess the causal relationship between exposure and outcome in epidemiological analysis (Lee and Lim, 2019;Richmond and Davey, 2022).…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota and common gastrointestinal diseases: a bidirectional two-sample Mendelian randomized study

Qiu,

Shen,

Yang

et al. 2023

Front. Microbiol.

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BackgroundSeveral recent studies have shown an association between gut microbiota and gastrointestinal diseases. However, the causal relationship between gut microbiota and gastrointestinal disorders is unclear.MethodsWe assessed causal relationships between gut microbiota and eight common gastrointestinal diseases using Mendelian randomization (MR) analyses. IVW results were considered primary results. Cochrane’s Q and MR-Egger tests were used to test for heterogeneity and pleiotropy. Leave-one-out was used to test the stability of the MR results, and Bonferroni correction was used to test the strength of the causal relationship between exposure and outcome.ResultsMR analyses of 196 gut microbiota and eight common gastrointestinal disease phenotypes showed 62 flora and common gastrointestinal diseases with potential causal relationships. Among these potential causal relationships, after the Bonferroni-corrected test, significant causal relationships remained between Genus Oxalobacter and CD (OR = 1.29, 95% CI: 1.13–1.48, p = 2.5 × 10–4, q = 4.20 × 10–4), and between Family Clostridiaceae1 and IBS (OR = 0.9967, 95% CI: 0.9944–0.9991, p = 1.3 × 10–3, q = 1.56 × 10–3). Cochrane’s Q-test showed no significant heterogeneity among the various single nucleotide polymorphisms (SNPs). In addition, no significant level of pleiotropy was found according to the MR-Egger.ConclusionThis study provides new insights into the mechanisms of gut microbiota-mediated gastrointestinal disorders and some guidance for targeting specific gut microbiota for treating gastrointestinal disorders.

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The challenge of Mendelian randomization approach

Cited by 8 publications

References 15 publications

The immune factors have complex causal regulation effects on inflammatory bowel disease

The immune factors have complex causal regulation effects on inflammatory bowel disease

Application and discoveries of metabolomics and proteomics in the study of female infertility

Gut microbiota and common gastrointestinal diseases: a bidirectional two-sample Mendelian randomized study

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