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Power calculation for the general two-sample Mendelian randomization analysis.

ABSTRACT: Mendelian randomization (MR) study has become a powerful approach to assess the potential causal effect of a risk exposure on an outcome. Most current MR studies are conducted under the two-sample setting by combining summary data from two separate genome-wide association studies (GWAS), with one providing measures on associations between genetic markers and the risk exposure, and the other on associations between genetic markers and the outcome. We develop a power calculation procedure for the general two-sample MR study, allowing for the use of multiple genetic markers, and shared participants between the two GWAS. This procedure requires a few easy-to-interpret parameters and is validated through extensive simulation studies.

SUBMITTER: Deng L

PROVIDER: S-EPMC8766247 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Power calculation for the general two-sample Mendelian randomization analysis.

Deng Lu L Zhang Han H Yu Kai K

Genetic epidemiology 20200211 3

Mendelian randomization (MR) study has become a powerful approach to assess the potential causal effect of a risk exposure on an outcome. Most current MR studies are conducted under the two-sample setting by combining summary data from two separate genome-wide association studies (GWAS), with one providing measures on associations between genetic markers and the risk exposure, and the other on associations between genetic markers and the outcome. We develop a power calculation procedure for the ...[more]

PMID: 32048336

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Project description:BackgroundAlthough observational studies suggest a correlation between psoriasis (PS) and cancers, it is still unknown whether this association can replace causal relationships due to the limitations of observational studies. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between PS and cancers.MethodsPS genetic summary data were obtained from two genome-wide association studies (GWAS). We employed MR Base for individuals retrieving tumors from distinct locations. Inverse-variance weighted analysis was the principal method used for MR, supplemented by weighted median, MR Egger, simple mode, and weighted mode. To investigate the possible link between psoriasis and cancers, we performed two independent two-sample MR studies and a meta-analysis based on two independent MR analyses.ResultsTwo independent MR analyses both found no significant causal relationship between PS and overall cancers (OR=1.0000, 95% confidence interval [CI]:0.9999-1.0001, P=0.984; OR=1.0000, 95% CI:0.9999-1.0001, P=0.761), and no significant causal relationship with 17 site-specific cancers. In the meta-analysis conducted by two two-sample MR analyses, there was no significant causal relationship between PS and overall cancers (OR=1.0000, 95% CI: 0.9999-1.0001, P=1.00, I 2 = 0.0%), and there was no significant causal relationship with 17 site-specific cancers.ConclusionsOur findings do not support a genetic link between PS and cancers. More population-based and experimental investigations will be required better to understand the complicated relationship between PS and cancers.

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Association between hypothyroidism and nephrotic syndrome: a bidirectional two-sample Mendelian randomization analysis.

Project description:BackgroundThere is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known.ObjectiveUsing pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis.MethodsSingle-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results.ResultsGenetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07-1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10-1.68, p = 0.01), and the MR-Egger intercept (intercept = -0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran's Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00-1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98-1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran's Q test (p = 0.61) and leave-one-out test results supported the robustness of the results.ConclusionHypothyroidism status could increase the risk of developing NS.

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Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis.

Project description:BackgroundPrevious epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis.MethodsWe performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.ResultsGenetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method.ConclusionsThis study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.

| S-EPMC10318899 | biostudies-literature

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