Jack Bowden is supported by an MRC Methodology Research Fellowship (grant MR/L012286/1). Stephen Burgess is supported by the Wellcome Trust (grant number 100114). George Davey Smith directs the MRC Integrative Epidemiology Unit supported by the MRC and the University of Bristol (MC_UU_12013_2, MC_UU_12013_5 and MC_UU_12013_8).