Egger-class {MendelianRandomization}

Egger Class

Description

An object containing the estimate produced using the MR-Egger method as well as various statistics.

The MR-Egger model uses a random-effects model; a fixed-effect model does not make sense as pleiotropy leads to heterogeneity between the causal estimates targeted by the genetic variants. The (multiplicative) random-effects model allows over-dispersion in the regression model. Under-dispersion is not permitted (in case of under-dispersion, the residual standard error is set to 1).

Slots

Model

Model always takes the value random, as only random-effects analyses are permitted.

Exposure

The name of the exposure variable.

Outcome

The name of the outcome variable.

Correlation

The matrix of correlations between genetic variants.

Robust

Whether robust regression was used in the regression model relating the genetic associations with the outcome and those with the exposure.

Penalized

Whether weights in the regression model were penalized for variants with heterogeneous causal estimates.

Estimate

The causal point estimate from the MR-Egger method.

StdError.Est

The standard error associated with Estimate.

Pvalue.Est

P-value associated with the causal estimate from the Wald method.

CILower.Est

The lower bound of the confidence interval for Estimate based on StdError.Est.

CIUpper.Est

The upper bound of the confidence interval for Estimate based on StdError.Est.

Intercept

The intercept estimate from the MR-Egger method. Under the InSIDE assumption, the intercept represents the average pleiotropic effect (average direct effect on the outcome) of a genetic variant. If the intercept differs from zero, this is evidence that the genetic variants are not all valid instruments; specifically, there is directional pleiotropy.

StdError.Int

The standard error associated with Intercept.

Pvalue.Int

P-value associated with the intercept from the Wald method.

CILower.Int

The lower bound of the confidence interval for Intercept based on StdError.Int.

CIUpper.Int

The upper bound of the confidence interval for Estimate based on StdError.Int.

Alpha

The significance level used in constructing the confidence interval (default is 0.05).

SNPs

The number of SNPs that were used in the calculation.

Causal.pval

P-value associated with the causal estimate.

Pleio.pval

P-value associated with the intercept (p-value for the MR-Egger intercept test of directional pleiotropy).

RSE

The estimated residual standard error from the regression model.

Heter.Stat

Heterogeneity statistic (Cochran's Q statistic) and associated p-value: the null hypothesis is that the MR-Egger regression model describes the associations with the outcome with no excess heterogeneity.

I.sq

A measure of heterogeneity between the genetic associations with the exposure (see Bowden IJE 2016: "Assessing the suitability of summary data for Mendelian randomization analyses using MR-Egger regression: The role of the I2 statistic."). Low values of I.sq relate both to large differences in precision between MR-Egger and IVW estimates, and to more weak instrument bias (in a two-sample setting, this is attenuation of MR-Egger estimate towards the null).