Table 5 Assumptions of the Study Designs and Action Taken to Satisfy Them

Absence of unmeasured or residual confounding

Inclusion of potential confounders in analysis models

Absence of pleiotropic effects that influence outcome

Use of genetic instruments associated with exposure at genome-wide significance level; assessment of pleiotropy in the IVW estimate; comparison of IVW estimate with those of sensitivity analyses more robust to pleiotropic effects; assessment of consistency of instrument effects

Absence of reverse causation

Assessment of anxiety exposures prior to most common period of AN onset

Absence of association between genetic instrument and confounders of exposure-outcome association

Use of genetic instruments associated with exposure at genome-wide significance level; assessment of consistency of instrument effects; use of GWAS completed in European samples only

Missing data does not depend on unobserved data

Imputation of missing data; inclusion of predictors of missingness in imputation and analysis models;

comparison of models with imputed, maximum available and complete case data

Robust association between genetic instrument and exposure

Use of genetic instruments associated with exposure at genome-wide significance level