Dataset Information

A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer.

ABSTRACT:

Background

Significantly rising plasma circulating C-reaction protein (CRP) concentrations are pervasive in lung cancer (LC) development, demonstrating a bidirectional relation. However, it remains uncertain whether the causation between them exists, and the degree to which the effect varies across different ethnic ancestries remains unknown. Therefore, we attempted to investigate the causal relationship between these two phenotypes.

Methods

With summary statistics of CRP-related single nucleotide polymorphisms (SNPs) identified by several large-scale genome-wide association studies (GWAS) datasets based on five ethnic ancestries coverage worldwide, we implemented bidirectional two-sample Mendelian randomization (MR) analyses. Genetic summary data of 11,348 LC cases and 15,861 controls from the International Lung Cancer Consortium (ILCCO) were applied. The inverse-variance weighted (IVW) approach was utilized as the principal analysis, supplemented by various complementary methods.

Results

MR study did not reveal the causal relationship shared across genetically predisposed CRP blood concentrations and LC risk (OR =1.022, 95% CI: 0.965-1.083, P=0.455) including pathological subtypes (OR =1.026, 95% CI: 0.947-1.112, P=0.534 for lung adenocarcinoma; OR =1.060, 95% CI: 0.970-1.158, P=0.201 for squamous cell lung cancer). Further analyses among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian populations revealed consistent null causation. Additionally, the causal effects of LC on CRP concentrations were not statically significant (OR =0.999, 95% CI: 0.977-1.021, P=0.923).

Conclusions

We did not observe a bidirectional causal association between CRP blood concentrations on LC among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian ancestry individuals.

SUBMITTER: Wu XR

PROVIDER: S-EPMC8743525 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer.

Wu Xiang-Rong XR Peng Hao-Xin HX Xiong Shan S Wen Yao-Kai YK Chen Jia-Na JN Li Cai-Chen CC Jiang Yu Y Su Zi-Xuan ZX Liu Jun J He Jian-Xing JX Liang Wen-Hua WH Cai Xiu-Yu XY

Translational lung cancer research 20211201 12

<h4>Background</h4>Significantly rising plasma circulating C-reaction protein (CRP) concentrations are pervasive in lung cancer (LC) development, demonstrating a bidirectional relation. However, it remains uncertain whether the causation between them exists, and the degree to which the effect varies across different ethnic ancestries remains unknown. Therefore, we attempted to investigate the causal relationship between these two phenotypes.<h4>Methods</h4>With summary statistics of CRP-related ...[more]

PMID: 35070748

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Project description:BackgroundPostpartum depression is the most common psychiatric disorder in pregnant women during the postpartum period and requires early detection and treatment. Previous studies have found that opioids use affects depression and anxiety disorders. Although it has long been suspected that opioids may contribute to the development of postpartum depression, observational studies are susceptible to confounding factors and reverse causality, making it difficult to determine the direction of these associations.MethodsTo examine the causal associations between opioids and non-opioid analgesics with postpartum depression, we utilized large-scale genome-wide association study (GWAS) genetic pooled data from two major databases: opioids, salicylate analgesic, non-steroidal anti-inflammatory drugs (NSAIDs), and aniline analgesics GWAS data from the United Kingdom Biobank database. GWAS data for postpartum depression were obtained from the FinnGen database. The causal analysis methods used random-effects inverse variance weighting (IVW), and complementary sensitivity analyses using weighted median, MR-Egger method, and MR-PRESSO test.ResultsIn the IVW analysis, Mendelian randomization (MR) analysis showed that opioids increased the risk of postpartum depression (OR, 1.169; 95% CI, 1.050-1.303; p = 0.005). Bidirectional analysis showed a significant causal relationship between genetically predicted postpartum depression and increased risk of opioids and non-opioid analgesics use (opioids OR, 1.118; 95% CI, 1.039-1.203; p = 0.002; NSAIDs OR, 1.071; 95% CI, 1.022-1.121; p = 0.004; salicylates OR, 1.085; 95% CI, 1.026-1.146; p = 0.004; and anilides OR, 1.064; 95% CI, 1.018-1.112; p = 0.006). There was no significant heterogeneity or any significant horizontal pleiotropy bias in the sensitivity analysis.ConclusionOur study suggests a potential causal relationship between opioids use and the risk of postpartum depression. Additionally, postpartum depression is associated with an increased risk of opioids and non-opioid analgesics use. These findings may provide new insights into prevention and intervention strategies for opioids abuse and postpartum depression.

Dataset Information

A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer.

Background

Methods

Results

Conclusions

Publications

A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer.

Similar Datasets

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