Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study

Yang, Hong; Song, Jié; Li, Aole; Lv, Linshuoshuo; Sun, Xiaohui; Mao, Yingying; Ye, Ding

doi:10.3389/fimmu.2023.1139799

Cited by 8 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, the Wald ratio was calculated for exposures with only one SNP, while IVW was utilized in cases where the exposure was associated with more than one SNP [ 21 ]. Additionally, in situations where the SNPs exhibited substantial heterogeneity, the IVW method with multiplicative random effects was used, otherwise IVW with fixed effects was applied [ 22 ]. Cochran’s Q statistic was calculated to evaluate the heterogeneity and provide evidence for invalid instruments ( P < 0.05) [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study

Fang,

Cao,

2024

Eur J Med Res

View full text Add to dashboard Cite

Background Intracranial aneurysm (IA) accounts for a substantial source of non-traumatic subarachnoid hemorrhage, with inflammation postulated as a potential factor in its pathogenesis. The present study aims at evaluating the association between circulating inflammatory cytokines and risk of IA under a bidirectional two-sample Mendelian randomization (MR) design. Methods For primary analysis, summary statistics of inflammatory regulators was obtained from a genome-wide association study (GWAS) comprising 8293 Finnish participants. Summary data of IA were extracted from a GWAS which comprised 7495 cases and 71,934 controls in European descent. For targeted analysis, summary statistics were extracted from two proteomic studies, which recruit 3301 and 5368 European participants, respectively. Summary data of IA were acquired from FinnGen study with 5342 cases and 342,673 controls. We employed inverse variance weighted (IVW) method as main approach, with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. Reverse MR analyses were conducted to minimize bias from reverse causality. Results No causation of cytokines with IA subtypes was identified in both primary and targeted analysis after Bonferroni correction. In primary analysis, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic (bFGF) levels were suggestively associated with aneurysmal subarachnoid hemorrhage (aSAH) [VEGF → aSAH: OR = 1.15, 95%CI 1.04–1.26, P = 0.005; bFGF → aSAH: OR = 0.62, 95% CI 0.42–0.92, P = 0.02]. Statistical significance failed to replicate in targeted analysis. Instead, suggestive protective effects for aSAH were identified in FGF-9 (FGF-9 → aSAH: OR = 0.74, 95% CI 0.62–0.89, P = 0.001) and FGF-16 (FGF-16 → aSAH: OR = 0.84, 95% CI 0.72–0.97, P = 0.017). Furthermore, reverse analyses identified suggestive effect of unruptured IA on RANTES, MIF, GRO-alpha, FGF-16, and FGF-19. Result remained robust after applying sensitivity tests. Conclusions No causality of inflammatory biomarkers on the risk of IA subtypes was identified. Future large-scale studies are in need to evaluate the temporal dynamics of cytokines in conjunction with IA.

show abstract

Section: Methodsmentioning

confidence: 99%

Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study

Fang,

Cao,

2024

Eur J Med Res

View full text Add to dashboard Cite

show abstract

“…Additionally, in situations where the SNPs exhibited substantial heterogeneity, the IVW method with multiplicative random effects was used, otherwise IVW with xed effects was applied [22]. Cochran's Q statistic was calculated to evaluate the heterogeneity and provide evidence for invalid instruments (P < 0.05) [23].…”

Section: Mendelian Randomization Analysismentioning

confidence: 99%

Circulating Inflammatory Biomarkers and Risk of Intracranial Aneurysm: A Mendelian Randomization Study

Fang

Cao

2023

Preprint

View full text Add to dashboard Cite

Background Intracranial aneurysm (IA) accounts for a substantial source of non-traumatic subarachnoid hemorrhage, with inflammation postulated as a potential factor in its pathogenesis. The present study aims at evaluating the association between circulating inflammatory cytokines and risk of IA under a bidirectional two-sample Mendelian randomization (MR) design. Methods For primary analysis, summary statistics of inflammatory regulators was obtained from a genome-wide association study (GWAS) comprising 8,293 Finnish participants. Summary data of IA was extracted from a GWAS which comprised 7,495 cases and 71,934 controls in European descent. For targeted analysis, summary statistics were extracted from two proteomic studies, which recruit 3,301 and 5,368 European participants, respectively. Summary data of IA were acquired from FinnGen study with 5,342 cases and 342,673 controls. We employed inverse variance weighted (IVW) method as main approach, with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. Reverse MR analyses were conducted to minimize bias from reverse causality. Results No causation of cytokines with IA was identified in both primary and targeted analysis after Bonferroni correction. In primary analysis, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic (bFGF) levels were suggestively associated with IA [(VEGF→IA: odds ratio (OR) = 1.11, 95% confidence interval (95% CI) = 1.02–1.20, P = 0.01; bFGF→IA: OR = 0.68, 95% CI = 0.48–0.96, P = 0.03]. Statistical significance failed to replicate in targeted analysis. Instead, suggestive protective effects for aneurysmal subarachnoid hemorrhage (aSAH) were identified in FGF-9 (FGF-9→aSAH: OR = 0.74, 95% CI = 0.62–0.89, P = 0.001) and FGF-16 (FGF-16→aSAH: OR = 0.84, 95% CI = 0.72–0.97, P = 0.017). Furthermore, reverse analyses identified suggestive effect of IA and its subtypes on IL-10, RANTES, MIF, GRO-alpha, FGF-16, and FGF-19. Result remained robust after applying sensitivity tests. Conclusions Our study provided novel insights into the potential protective role of FGF-9 and FGF-16 in aSAH. Future studies are in need to evaluate the temporal dynamics of cytokines in conjunction with IA.

show abstract

Understanding the Genetic Architecture of Vitamin Status Biomarkers in the Genome-Wide Association Study Era: Biological Insights and Clinical Significance

Reay,

Clarke,

Albiñana

et al. 2024

Advances in Nutrition

View full text Add to dashboard Cite

Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study

Cited by 8 publications

References 35 publications

Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study

Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study

Circulating Inflammatory Biomarkers and Risk of Intracranial Aneurysm: A Mendelian Randomization Study

Understanding the Genetic Architecture of Vitamin Status Biomarkers in the Genome-Wide Association Study Era: Biological Insights and Clinical Significance

Contact Info

Product

Resources

About