Corrigendum: Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study.
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ABSTRACT:
SUBMITTER: Liang Y
PROVIDER: S-EPMC8632056 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionFibroblast growth factor 23 (FGF23), a potential biomarker for kidney function, is related to cardiovascular disease (CVD) and diabetes, although it is unclear whether the relation is causal. This study evaluated the associations of genetically predicted FGF23 with major CVDs, their risk factors, kidney function, and longevity using Mendelian randomization (MR).MethodsThis is a two-sample MR study using summary statistics from large genome-wide association studies. Primary outcomes included coronary artery disease (CAD), myocardial infarction, heart failure, and atrial fibrillation. Secondary outcomes included cardiovascular risk factors, kidney function, and longevity. We used four single-nucleotide polymorphisms (SNPs) predicting FGF23, excluding rs2769071 in the ABO gene, which likely violates the MR exclusion-restriction assumption. We used inverse-variance weighted (IVW) as the primary statistical method to assess associations of FGF23 with the outcomes. Sensitivity analyses included weighted median (WM) and MR-Egger. We repeated the analyses including all five SNPs. Last, we validated the positive findings from the main analyses in a smaller study, i.e., FinnGen.ResultsUsing IVW, genetically predicted higher FGF23 was inversely associated with risk of CAD [odds ratio (OR): 0.69 per logtransformed FGF23 (pg/ml) increase, 95% confidence interval (CI): 0.52-0.91] and type 2 diabetes mellitus (T2DM) (OR: 0.70, 95% CI: 0.52-0.96), but not with the other outcomes. The WM and MR-Egger estimates were directionally consistent.ConclusionThis study suggests that genetically predicted higher FGF23 may be protective against CAD and T2DM. Future studies should explore the underlying mechanisms related to the potential protective effect of FGF23. FGF23 was unlikely a cause of poorer renal function.
| S-EPMC8343174 | biostudies-literature
Project description:ObjectiveIn observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men.MethodsWe performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty.ResultsGenetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers.ConclusionThis study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.
| S-EPMC9730605 | biostudies-literature
Project description:BackgroundPrevious studies have found atrial fibrillation (AF) is associated with valvular heart disease (VHD). However, whether there is a causal relationship between these two diseases or it is just a result of bias caused by confounding factors is uncertain. This study aims to examine the potential causal association between AF and VHD by using Mendelian randomization.MethodsIn order to examine the causal relationship between AF and VHD, we performed a two-sample Mendelian randomization study by collecting exposure and outcome data from genome-wide association study (GWAS) datasets. We utilized data from FinnGen project (FinnGen, 11,258 cases for VHD including rheumatic fever, 3,108 cases for non-rheumatic VHD, and 75,137 cases for participants) and European Bio-informatics Institute database (EBI, 55,114 cases for AF and 482,295 cases for participants). Inverse-variance weighted (IVW), MR-Egger, and weighted median approaches were performed to estimate the causal effect.ResultsThe Mendelian randomization analysis indicated that AF increased the risk of VHD by all three MR methods [For VHD including rheumatic fever: IVW, odds ratio (OR) = 1.255; 95% confidence interval (CI), 1.191~1.322; p = 1.23 × 10-17; Weighted median, OR = 1.305, 95% CI, 1.216~1.400, p = 1.57 × 10-13; MR-Egger, OR = 1.250, 95% CI, 1.137~1.375, p = 1.69 × 10-5; For non-rheumatic VHD: IVW, OR = 1.267; 95% CI, 1.169~1.372; p = 6.73 × 10-9; Weighted median, OR = 1.400; 95% CI, 1.232~1.591; p = 2.40 × 10-7; MR-Egger, OR = 1.308; 95% CI, 1.131~1.513; p = 5.34 × 10-4]. After the one outlier SNP was removed by heterogeneity test, the results remained the same. No horizontal pleiotropic effects were observed between AF and VHD.ConclusionsOur study provides strong evidence of a causal relationship between AF and VHD. Early intervention for AF patients may reduce the risk of developing into VHD.
| S-EPMC8996053 | biostudies-literature
Project description:To investigate the causal relationship between circulating serum homocysteine (Hcy) levels and osteoporosis (OP). Using public datasets gathered from independently published genome-wide association studies (GWAS), Mendelian randomization (MR) analysis was done to investigate the causal influence of Hcy on OP. SNPs were selected from a meta-analysis of GWAS on Hcy concentrations in 44,147 individuals of European ancestry. Meanwhile, SNPs of individuals of European descent for OP were extracted from the Genetic Factors of Osteoporosis Consortium (GEFOS) UK Biobank. The odds ratio (OR) of inverse variance weighted (IVW) approaches was established as the primary outcome. Moreover, weighted median (WM) and MR-Egger regressions were included in the sensitivity analysis. There were no causal effects of Hcy on forearm bone mineral density and lumbar bone mineral density according to IVW, MR-Egger, and WM analyses (all p > 0.05). In the IVW, we discovered the causality between genetically predicted Hcy and heel bone mineral density (H-BMD) with an OR of 0.96 [95% confidence interval (CI) = 0.927-0.990, p = 0.011]. In the additional sensitivity analysis, WM regression (OR = 0.97, 95% CI = 0.995-1.076, p = 0.084) and MR-Egger regression (OR = 0.98, 95% CI = 0.918-1.049, p = 0.609) yielded values that were comparable in direction but less precise. The MR-Egger intercept, funnel plot, and IVW all indicate the absence of any discernible directional pleiotropy. The leave-one-out analysis revealed that a single SNP did not influence the results of the MR analysis. In conclusion, our MR investigation revealed evidence of a causal relationship between circulating serum Hcy levels and H-BMD, but not OP in the European population. However, larger sample sizes are needed in the future to get more reliable conclusions.
| S-EPMC10239750 | biostudies-literature
Project description:This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90-0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86-0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94-1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association.
| S-EPMC10570324 | biostudies-literature
Project description:BackgroundAlthough numerous observational studies have indicated a potential association between autoimmune diseases, such as rheumatoid arthritis (RA) and alopecia areata (AA), the research reports lack a clear causal relationship. In this study, our objective is to utilize the Mendelian randomization (MR) design to examine the potential causal association between RA and AA.MethodsTo investigate the causal relationship between RA and AA, we utilized large-scale gene aggregation data from genome-wide association studies (GWAS), including RA (n=58,284) and AA (n=361,822) based on previous observational studies. In our analysis, we mainly employed the inverse variance-weighted (IVW) method of the random effects model, supplemented by the weighted median (WM) method and the MR Egger method.ResultsThe findings from the IVW methods revealed a significant association between genetically predicted RA and an increased likelihood of AA, as evidenced by an odds ratio of 1.21 (95%CI = 1.11-1.32; P < 0.001. Both the WM method and MR-Egger regression consistently showed significant directional outcomes (Both P < 0.05), indicating a robust association between RA and AA. Additionally, both the funnel plot and the MR-Egger intercepts provided evidence of the absence of directional pleiotropy, suggesting that the observed association is not influenced by other common genetic factors.ConclusionsThe results of the study suggest a possible link between genetically predicted RA and AA. This finding highlights the importance for individuals diagnosed with RA to remain vigilant and aware of the potential development of AA. Regular monitoring and early detection can be crucial in managing and addressing this potential complication.
| S-EPMC10644376 | biostudies-literature
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.
| S-EPMC10808795 | biostudies-literature
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.
| S-EPMC10999687 | biostudies-literature
Project description:Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10-4), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10-4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.
| S-EPMC8639868 | biostudies-literature
Project description:BackgroundThe most commonly acknowledged non-scarring alopecia are androgenetic alopecia (AGA) and alopecia areata (AA). Previous studies have revealed various risk factors associated with alopecia. However, the relationship between leukocyte telomere length (LTL) and non-scarring alopecia remains unclear.MethodsA two-sample Mendelian randomization (MR) analysis was performed to evaluate the causality between genetically predicted LTL and the risk of non-scarring alopecia. MR analyses were performed using the inverse variance-weighted (IVW) method and complemented with other MR methods.ResultsThe summary statistics of the genome-wide association studies (GWAS) for AGA and AA were obtained from the FinnGen biobank, which included 119,185 and 211,428 individuals, respectively. A total of 126 single nucleotide polymorphisms (SNPs) with genome-wide significance were selected as the instrumental variables for LTL. The MR analyses suggested a causal relationship between LTL and AGA, and the risk of AGA increased by 3.19 times as the genetically predicted LTL was shortened by one standard deviation in log transformed form under the IVW method (OR = 4.19, 95% CI = 1.20-14.61, p = 0.024). The other MR methods also demonstrated a similar trend of the effect of LTL on AGA. There was no causal relationship between LTL and AA (p > 0.05). Sensitivity analyses further demonstrated that the current results were less likely to be affected by confounders and bias.ConclusionOur results suggested a potential causal relationship between LTL and AGA, and shortened LTL was associated with an increased risk of AGA.
| S-EPMC9926966 | biostudies-literature