Mendelian randomization rules out the causal relationship between serum lipids and cholecystitis

Yang, Hongqun; Chen, Lanlan; Liu, Kaiyu; Li, Chengnan; Li, Haitao; Xiong, Kezhen; Li, Zehan; Lu, Chunxia; Chen, Wei; Liu, Yahui

doi:10.1186/s12920-021-01082-y

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…Considering that these genetic variants are associated with exposure, MR analysis is a method of natural randomization and is not subject to confounding factors ( Emdin et al, 2017 ). Mendelian randomization studies are, therefore, more convincing and reliable than traditional observational studies ( Yang et al, 2021 ). They are widely used in the detection of causality in the onset of disease.…”

Section: Introductionmentioning

confidence: 99%

A mendelian randomization study with populations of European ancestry rules out a causal relationship between inflammatory bowel disease and colorectal cancer

Liu²,

Wang³

et al. 2022

Front. Genet.

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Background: Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has been found to be associated with colorectal cancer (CRC) in observational studies, but there is no evidence to support a causal relationship or reverse causality between the two diseases.Methods: We employed two-sample bidirectional Mendelian randomization to estimate an unconfounded bidirectional causal relationship between IBD (including UC and Crohn’s disease (CD)) and colorectal cancer. After searching IEU GWAS database and filtering SNPs, we applied a variety of MR methods including IVW method using qualified instrumental variables, and conducted sensitivity analysis to detect the heterogeneity and pleiotropy of instrumental variables.Results: After using three groups of SNPs (CD: 106, UC: 113, IBD: 70), the IVW method MR analysis showed that the results were not significant (result for UC: odds ratio (OR) [95% Confidence Interval (CI)]: 0.9998 [0.9991–1.0005], p value: 0.58; result for CD: OR [95%CI]: 0.99962 [0.99912–1.00012], p value: 0.14; results for IBD: OR [95%CI]: 0.99959 [0.99869–1.00048], p value: 0.36). MR-Egger regression, WM method and MR-RAPS method reached the same conclusion. Sensitivity analysis did not reveal heterogeneity and pleiotropy. Bidirectional MR analysis was performed using the same procedure, and the results of IVW MR analysis were also not significant (result for CD: OR [95%CI]: 1.07985 [0.00049–2372.38304], p value 0.98; result for UC: OR [95%CI]: 0.27117 [0.00014–528.3707], p value: 0.74; result for IBD: OR [95%CI]: 0.47101 [0.0001–2242.94159], p value: 0.86). MR-Egger regression, WM method and MR-RAPS method also reached the same conclusion. Sensitivity analysis did not find any evidence of heterogeneity and pleiotropy.Conclusion: Contrary to the conclusions of previous observational studies, a two-sample MR analysis did not find a causal relationship or reverse causal relationship between IBD and CRC. Sporadic CRC (sCRC) may differ in pathogenesis from IBD-related CRC.

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Section: Introductionmentioning

confidence: 99%

A mendelian randomization study with populations of European ancestry rules out a causal relationship between inflammatory bowel disease and colorectal cancer

Liu²,

Wang³

et al. 2022

Front. Genet.

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“…We excluded individuals with missing data from the analysis. The exclusion criteria were subjects who had been diagnosed with fatty liver or cholecystitis [30][31][32]. After exclusion, 47,562 participants remained, as shown in Figure 1.…”

Section: Participantsmentioning

confidence: 99%

Associations between the Genetic Heritability of Dyslipidemia and Dietary Patterns in Korean Adults Based on Sex Differences

Kim,

Jeon,

Lee

et al. 2023

Nutrients

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Dyslipidemia can be defined as an abnormality in serum lipid levels that is substantially linked to genetic variations and lifestyle factors, such as diet patterns, and has distinct sex-specific characteristics. We aimed to elucidate the genetic impact of dyslipidemia according to sex and explore the associations between genetic variants and dietary patterns in large-scale population-based cohorts. After performing genome-wide association studies (GWASs) in male, female, and entire cohorts, significant single nucleotide polymorphisms (SNPs) were identified in the three groups, and genetic risk scores (GRSs) were calculated by summing the risk alleles from the selected SNPs. After adjusting for confounding variables, the risk of dyslipidemia was 2.013-fold and 2.535-fold higher in the 3rd quartile GRS group in the male and female cohorts, respectively, than in the 1st quartile GRS group. While instant noodle and soft drink intake were significantly associated with GRS related to hyperlipidemia in male cohorts, coffee consumption was substantially related to GRS related to hyperlipidemia in female cohorts. Considering the influence of genetic factors and dietary patterns, the findings of this study suggest the potential for implementing sex-specific strategic interventions to avoid dyslipidemia.

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“…Although experimental research can make up for many of the limitations of observational research, experimental design and implementation must be both precisely specified and strictly controlled, rendering it difficult to implement. Because the implementation of experimental research must consider ethics, it is often difficult to use this method to directly study the etiology of diseases ( 18 ). Mendelian randomization (MR) has been proposed as a method for overcoming these limitations.…”

Section: Introductionmentioning

confidence: 99%

Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study

Gou,

Li,

Qiao

et al. 2023

Front. Nutr.

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BackgroundInsulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).MethodsTwo-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.ResultsGenetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW β:0.021, 95% CI: 0.005–0.036, p = 7.74 × 10–3; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, p = 2.50 × 10–7). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW β:0.182, 95% CI: 0.061–0.305, p = 3.25 × 10–3; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, p = 4.73 × 10–3). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept p = 5.1 × 10–5, 25-OHD intercept p = 6.4 × 10–4 in forward analysis; Vit D intercept p = 6.6 × 10–4, 25-OHD intercept p = 1.9 × 10–3 in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.ConclusionThe results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.

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Mendelian randomization rules out the causal relationship between serum lipids and cholecystitis

Cited by 4 publications

References 30 publications

A mendelian randomization study with populations of European ancestry rules out a causal relationship between inflammatory bowel disease and colorectal cancer

A mendelian randomization study with populations of European ancestry rules out a causal relationship between inflammatory bowel disease and colorectal cancer

Associations between the Genetic Heritability of Dyslipidemia and Dietary Patterns in Korean Adults Based on Sex Differences

Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study

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