Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population

Zhang, Jun

doi:10.2147/jir.s354619

Cited by 15 publications

(16 citation statements)

References 41 publications

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“…In addition, compared with observational epidemiological studies, MR analysis does not involve high measurement costs or a large number of appropriate biospecimens (16). Therefore, MR analysis has high reliability and is widely used in many studies (17,47).…”

Section: Discussionmentioning

confidence: 99%

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

Ma²,

Zhang³

et al. 2022

Front. Endocrinol.

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ObjectiveTo explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).MethodsPublicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR–Egger methods. The pleiotropy of MR results was determined using MR–Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results.ResultsBased on IVW, MR–Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR–Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.ConclusionOur results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.

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Section: Discussionmentioning

confidence: 99%

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

Ma²,

Zhang³

et al. 2022

Front. Endocrinol.

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“…Importantly, any outliers in the distortion test of MR-PRESSO analysis were excluded and the causal estimates were reassessed. Furthermore, we applied the radial variants of the IVW and MR Egger model to visualize the causal estimates, and they also can detect the outliers [ 56 ]. Moreover, the MR robust adjusted profile score (MR-RAPS) method was used to assess the causal relationship and validate the robustness of MR analysis [ 56 ].…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, we applied the radial variants of the IVW and MR Egger model to visualize the causal estimates, and they also can detect the outliers [ 56 ]. Moreover, the MR robust adjusted profile score (MR-RAPS) method was used to assess the causal relationship and validate the robustness of MR analysis [ 56 ]. The p > 0.05 indicated that it conformed to the normal distribution and the evaluation results had strong robustness.…”

Section: Methodsmentioning

confidence: 99%

No Evidence of a Genetic Causal Relationship between Ankylosing Spondylitis and Gut Microbiota: A Two-Sample Mendelian Randomization Study

et al. 2023

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Objective: Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of “parental alleles are randomly assigned to offspring” and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. Results: The random-effects IVW results showed that Bacteroides (p = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621–1.579]), Streptococcus (p = 0.591, OR 95% CI = 1.120 [0.741–1.692]), Proteobacteria (p = 0.522, OR 95% CI = 1.160 [0.737–1.826]), and Lachnospiraceae (p = 0.717, OR 95% CI = 1.073 [0.732–1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. Conclusion: This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.

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“…If the MR analysis results were affected by a single SNP, in order to prevent the occurrence of false positives or false negatives to the greatest extent, we carried out a second round of genetic assessment after deleting the single SNP that affected the MR analysis results. Moreover, the MR robust adjusted profile score (MR-RAPS) method was used to validate the robustness of the MR analysis ( 26 ). A P > 0.05 indicated that it conformed to the normal distribution and the evaluation results had strong robustness.…”

Section: Methodsmentioning

confidence: 99%

“…According to Mendelian laws of heredity, germline genetic information is randomly fixed at conception, and Mendelian randomization (MR) methods use genetic variations, such as single nucleotide polymorphisms (SNPs), as instrumental variables to assess genetic causality between traits and diseases or between diseases ( 26 ). MR analysis is not affected by confounding factors and reverse causality of traditional epidemiological methods, such as retrospective studies, and has been widely used ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study

et al. 2023

Front. Endocrinol.

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ObjectiveThe occurrence and development of oesophageal neoplasia (ON) is closely related to hormone changes. The aim of this study was to investigate the causal relationships between age at menarche (AAMA) or age at menopause (AAMO) and benign oesophageal neoplasia (BON) or malignant oesophageal neoplasia (MON) from a genetic perspective.MethodsGenome-wide association study (GWAS) summary data of exposures (AAMA and AAMO) and outcomes (BON and MON) were obtained from the IEU OpenGWAS database. We performed a two-sample Mendelian randomization (MR) study between them. The inverse variance weighted (IVW) was used as the main analysis method, while the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The maximum likelihood, penalized weighted median, and IVW (fixed effects) were validation methods. We used Cochran’s Q statistic and Rucker’s Q statistic to detect heterogeneity. The intercept test of the MR Egger and global test of MR pleiotropy residual sum and outlier (MR-PRESSO) were used to detect horizontal pleiotropy, and the distortion test of the MR-PRESSO analysis was used to detect outliers. The leave-one-out analysis was used to detect whether the MR analysis was affected by single nucleotide polymorphisms (SNPs). In addition, the MR robust adjusted profile score (MR-RAPS) method was used to assess the robustness of MR analysis.ResultsThe random-effects IVW results showed that AAMA had a negative genetic causal relationship with BON (odds ratio [OR] = 0.285 [95% confidence interval [CI]: 0.130-0.623], P = 0.002). The weighted median, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with random-effects IVW (P < 0.05). The MR Egger, simple mode and weighted mode results showed that AAMA had no genetic causal relationship with BON (P > 0.05). However, there were no causal genetic relationships between AAMA and MON (OR = 1.132 [95%CI: 0.621-2.063], P = 0.685), AAMO and BON (OR = 0.989 [95%CI: 0.755-1.296], P = 0.935), or AAMO and MON (OR = 1.129 [95%CI: 0.938-1.359], P = 0.200). The MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with a random-effects IVW (P > 0.05). MR analysis results showed no heterogeneity, the horizontal pleiotropy and outliers (P > 0.05). They were not driven by a single SNP, and were normally distributed (P > 0.05).ConclusionOnly AAMA has a negative genetic causal relationship with BON, and no genetic causal relationships exist between AAMA and MON, AAMO and BON, or AAMO and MON. However, it cannot be ruled out that they are related at other levels besides genetics.

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Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population

Cited by 15 publications

References 41 publications

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization

No Evidence of a Genetic Causal Relationship between Ankylosing Spondylitis and Gut Microbiota: A Two-Sample Mendelian Randomization Study

Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study

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