What can Mendelian randomization contribute to biological anthropology?

Bonilla, Carolina; Herrera, Guadalupe; Sans, Mónica

doi:10.1002/ajpa.24750

Cited by 4 publications

(1 citation statement)

References 75 publications

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“…The validity of the IV assumption is a prerequisite for causal inference when applying MR (26). MR offers a unique advantage in overcoming confounding and reverse causality issues commonly associated with traditional observational studies (27). As the amount of Genome-Wide Association Study (GWAS) data and the use of multiomics technologies continue to grow, the application of MR in causal inference is becoming increasingly widespread (28).…”

Section: Introductionmentioning

confidence: 99%

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Qin,

Yang,

Ning

2024

Shock

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Objective Several epidemiological studies have identified a potential link between serum uric acid(UA), gout and sepsis. The primary objective of this study is to delve deeper into this connection, investigating the causal effect of UA and gout on sepsis by applying Mendelian Randomization (MR). Methods The causal relationship was analyzed using data from genome-wide association study(GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Three complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple median method. Horizontal pleiotropy was identified by MR-Egger intercept test. Cochran’s Q statistics were employed to assess the existence of instrument heterogeneity. The leave-one-out method was used as a sensitivity analysis. Results The IVW results indicated that there was a positive causal relationship between UA and sepsis(critical care) (OR = 0.24, 95%CI: 0.04 to 0.43, P = 0.018, F = 4291.20). There was no significant association between UA and sepsis(28 day death in critical care) (OR = 0.10, 95%CI: -0.29 to 0.50, P = 0.604). There was no significant association between gout and sepsis(critical care) (OR = 0.85, 95%CI: -4.87 to 6.57, P = 0.771), and sepsis(28 day death in critical care) (OR = -6.30, 95%CI: -17.41 to 4.81, P = 0.267). Horizontal pleiotropy was absent in this study. The results were robust under all sensitivity analyses. Conclusion The study revealed that elevated UA levels was causally linked with sepsis(critical care). No causal relationship had been found between UA and sepsis(28 day death in critical care), as well as between gout and sepsis.

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Section: Introductionmentioning

confidence: 99%

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Qin,

Yang,

Ning

2024

Shock

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Diet, Metabolic Biomarkers, and Sensorineural Hearing Loss: A Mendelian Randomization and Mediation Analysis

Yang,

Luo,

Chen

2024

Preprint

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Sensorineural hearing loss (SNHL) is influenced by genetic and environmental factors. This study explores the causal relationships between dietary choices, circulating metabolic biomarkers, and SNHL using Mendelian Randomization (MR) analysis. We utilized summary statistics from genome-wide association studies (GWAS) on dietary choices and metabolic biomarkers as exposures, with SNHL as the outcome. Two-sample MR analysis and mediation analysis were conducted to identify causal links and metabolic pathways. The MR analysis revealed that fish, oily fish, healthy food, and vegetable consumption significantly reduce the risk of SNHL. The mediation analysis further indicated that these protective effects are mediated by the ratios of DHA, omega-3, and polyunsaturated fatty acids to total fatty acids, with DHA mediating approximately 10.57% of the protective effect of oily fish consumption. Significant causal pathways link dietary choices and metabolic biomarkers to SNHL, suggesting that dietary modifications, particularly increasing the intake of fish, healthy foods, and vegetables, could serve as effective preventive strategies against SNHL. This study provides valuable insights into the interplay between diet, metabolism, and hearing health, guiding future preventive strategies.

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The causal association between inflammatory bowel disease and breast cancer: a bidirectional two-sample Mendelian randomization study

Yin,

Zhang

2024

Front. Genet.

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Objective: This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC).Materials and Methods: We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and vice versa. The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses.Results: The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009–1.087; p = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn’s Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015–1.073; p = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer (p > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022–1.211; p = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) (p > 0.05). Genetic predictions indicate a positive effect of Crohn’s Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002–1.040; p = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032–1.168; p = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008–1.319; p = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations (p > 0.05).Conclusion: This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.

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What can Mendelian randomization contribute to biological anthropology?

Cited by 4 publications

References 75 publications

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Causal Roles of Serum Uric Acid Levels and Gout in Sepsis: A Mendelian Randomization Study

Diet, Metabolic Biomarkers, and Sensorineural Hearing Loss: A Mendelian Randomization and Mediation Analysis

The causal association between inflammatory bowel disease and breast cancer: a bidirectional two-sample Mendelian randomization study

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