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For SVMR, we also used, alternatively, Generalized single variable Summary-data based MR (GSMR) to identify and remove instruments with heterogeneous causal estimates suspected to be invalid instruments with apparent pleiotropic effects on both exposure and outcome disease (using the recommended default HEIDI (heterogeneity in dependent instruments) -outlier threshold (0.01) to retain sufficient power to detect heterogeneity) 91