Dataset Information

Genetically predicted bipolar disorder is causally associated with an increased risk of breast cancer: a two-sample Mendelian randomization analysis

ABSTRACT:

Background

Epidemiologic findings suggested that bipolar disorder (BD) may be associated with an increased risk of breast cancer. However, there are few studies that comprehensively evaluating their correlation and the causal effect remains unknown. With a two-sample Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods

Utilizing 14 BD-related single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. Study-specific estimates were summarized using inverse variance weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical types of breast cancer were also conducted.

Results

MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR =1.059; 95% CI: 1.008–1.112, P=0.0229). When results were examined by immunohistochemical type, no causal effects between genetically predicted BD and estrogen receptor (ER)-positive breast cancer (OR =1.049, 95% CI: 0.999–1.102 P=0.0556) and ER-negative breast cancer (OR =1.032, 95% CI: 0.953–1.116 P=0.4407) were observed. Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Conclusions

Our findings provided evidence for a causal relationship between genetically predicted BD and an increased risk of breast cancer overall. Further studies are warranted to investigate the underlying mechanism.

SUBMITTER: Peng H

PROVIDER: S-EPMC8033315 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveThe causal association between chronic rhinosinusitis (CRS) and stroke remains uncertain due to the susceptibility of observational studies to confounding and the possibility of reverse causality. This study aims to examine the potential causal relationship between CRS and the risk of stroke, encompassing various subtypes.MethodsIn this research, we utilized genome-wide association study (GWAS) data for CRS from FinnGen. We identified significant single-nucleotide polymorphisms (SNPs) associated with CRS and used them as instrumental variables (IVs). GWAS data for any ischemic stroke (AIS), ischemic stroke (IS), large-artery atherosclerotic stroke (LAS), small-vessel strokes (SVS), cardioembolic strokes (CES), intracerebral hemorrhage (ICH), lobar ICH, and non-lobar ICH came from multi-ancestry GWAS datasets. We conducted two-sample Mendelian randomization (MR) analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to investigate potential causal relationships between CRS and stroke. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.ResultThe IVW analysis revealed no significant associations between CRS and AIS (OR = 0.99, 95% CI [0.93-1.05], p = 0.73), IS (OR = 0.97, 95% CI [0.81-1.17], p = 0.09), SVS (OR = 0.96, 95% CI [0.82-1.12], p = 0.58), LAS (OR = 0.91, 95% CI [0.77-1.08], p = 0.09), CES (OR = 0.97, 95% CI [0.81-1.17], p = 0.79), ICH (OR = 1.28, 95% CI [0.74-2.22], p = 0.28), lobar ICH (OR = 1.22, 95% CI [0.60-2.50], p = 0.28), and non-lobar ICH (OR = 1.25, 95% CI [0.65-2.40], p = 0.79). Sensitivity analysis found no evidence of horizontal pleiotropy.ConclusionAccording to genetic evidence, this Mendelian randomization (MR) study does not indicate a causal relationship between CRS and stroke in European populations. However, further studies are necessary to comprehensively evaluate the potential association between CRS and stroke.

Project description:BackgroundObservational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive.MethodsIn this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness.ResultsThe IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods.ConclusionThis study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.