Title: Noodles, No Nulls and Numb Skulls: Threats to the future of Mendelian Randomisation

Abstract: Few Mendelian Randomisation (MR) papers were published in the first decade of its 20 year history, but since then there has been an exponential increase, which shows no sign of slowing down.  The vast majority of papers are, at best, uninformative, and at worst, nonsense.  In this seminar I will restate the fundamental assumption of MR, that of gene-environment equivalence, and the conditions for causal effect identification and estimation. I will then group the threats under three headings: (1) Noodles: papers that are prima facie nonsense, generated from easily available two sample MR data and sub–ChatGPT text (2) No Nulls: influential early MR findings suggested that some drug targets – such as HDL cholesterol level or C-reactive protein – were unlikely to be important. Null MR studies are now increasingly rarely seen (3) Numb Skulls: the simplicity of the MR approach is being obscured by increasingly complex methods, the assumptions of which will be opaque to most readers. The common source of these threats will be discussed, approaches to mitigating them advanced, and some promising future directions introduced

Biography: George Davey Smith was a member of the noise-terrorism outfit Scum Auxiliary in the early 1980s. Since artistic and commercial success eluded them, he has had to earn his living working as an epidemiologist in the provinces of the UK. In 2003 he and Shah Ebrahim published the first extended formalisation of Mendelian randomization as it is currently understood, and he is still on the circuit flogging this two decades on. 

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