george davey smith
@mendel_random
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Joined February 2012
1/n A webinar from @CDC_Genomics on Mendelian randomization (MR) highlights some under-appreciated aspects of MR; this thread outlines these
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I’m clearly suffering from memory loss as I have vague recall of 2020/1 when I thought some TV ⭐️ experts were resisting any relaxation of lockdowns. But apparently they weren’t & were worried about the terrible effects on kids. Will check myself in for cognitive function tests.
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Vaccine advice quiz: would you prefer to take advice from (1) a self-appointed group who fail to recognise SARS-CoV-2 is endemic 18 months after it became obvious (2) a due-process appointed group that actually consists of established vaccine experts?.
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Convalescent plasma therapy used in 100,000s of patients and Recovery trial now suggests no benefit & evidence grows that its use has contributed to emergence of new variants. Don't believe "real world evidence": RCTs essential to avoid unanticipated harms
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PNAS editor's rejection of paper that fails to replicate highly cited PNAS nonsense with 10x statistical power and vastly better phenotyping
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As things get better we see the ratcheting up of how "worrying", "very worrying" and "extremely worrying" the any signs of relaxation of restrictions are. Perhaps what's unbearably worrying is the potential disappearance of a daily TV & radio platform for expressing such worry?🤔.
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@MariaUloko Congrats to your dad! My dad who left school at minimum school leaving age in 1930s got a degree with the wonderful @OpenUniversity at 66, proudest (and super emotional) moment applauding as he collected his degree. Hope you can see him receive his degree in these weird times.
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Conferences/seminars have increasingly weird and restrictive rules on sharing what is said: here is a standard disclaimer for talks I give
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Trying to find the epidemiology textbook that says that every single form of study design is invalid and unethical, except for the use of fear-inducing floating numerators. Anyone any ideas which one it is?.
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China is abandoning its zero covid before the policy further destabilizes the country. In the UK as well as China a self-appointed group denied the scientific evidence, which is that there was no other prospect than SARS-CoV-2 becoming endemic /cont .
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Mendelian Randomisation (MR) is going to hell in a handcart, with an exponential weekly increase of papers with Mendelian Randomisation in the title, most of them nonsense. 25th April 4.30pm online or in person @ucl I'll talk about what should be done
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The late Doug Altman was the most generous & modest global (statistical) superstar you could ever meet, asked for an opinion of an idea he'd sound so positive it would take a while for you to realise he was gently explaining to you a fundamental flaw he'd instantly spotted.
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The massive promotion of some "experts" during covid by certain media, eg @guardian made some views, like "zero covid" - that were rejected by most scientists - appear rational. An ironic pairing here & short 🧵/cont … .
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I am extremely worried that not enough people are extremely worried.
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A reminder of the danger of “long placebo”.
Yikes, would you take a drug* with this side effect profile?!. (*oh, it's the placebo arm of the Pfizer vaccine trial)
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In 2018 we published a non-linear Mendelian randomisation (NLMR) study in @ObesitySociety and it is now clear the method we applied is deeply flawed, so in October we published a Perspective correcting it. A 🧵on the cautionary tale of NLMR
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2 years ago @IndependentSage said schools should not open until there was #ZeroCovid. Schools would still be shut today. If I've missed their apology for advocating further harm to the lives of disadvantaged kids, can someone point me to this apology?.
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"Epidemiology for the uninitiated" by Geoffrey Rose and others is now online @bmj_latest 🥳🎉The misleading "floating numerators" that were widely tweeted on eg long covid in children could have been avoided if their authors had read this.
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Our reply to a @bmj_latest "rapid response" to our editorial "Closing schools is not evidence based and harms children". Conclusion: a long list of signatories / ”co-authors” is no guarantee of accuracy @ProfSarahJLewis @apsmunro @AllysonPollock
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Finally Simpson’s paradox in a way even I can follow ….
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England playing in major international football tournaments increases heart attack deaths. We *must* stop such games for public health reasons. Will 121 people please join me in writing a letter to @lancet to ensure this outrage is stopped? .
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Brilliant seminar by Richard Peto @HarvardChanSPH about the influence of residual confounding in observational epidemiological studies. Compelling actual and hypothetical examples immediately suggest sensitivity analyses explicitly for this should be /cont
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This is the best single thing I’ve seen written on where we are with #COVID19 (and both interviews worth watching in full)
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As an elderly drunk epidemiologist I realise it’s fortunate I have no power
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Mendelian randomization explained in two minutes
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Paper in @bmj_latest shows ultraprocessed food consumption is associated with every adverse health outcome that poor people have higher risks of than the well healed. Here @MarcusMunafo explains why these associations should not be interpreted as causal
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"You cannot enjoy it" Zero covid explained in a brilliant dispatch by @TomHale_ from the Beijing Winter Olympics
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This was written 15th July 2020, the day after Sir David King, chair of @IndependentSage said schools should be kept shut till there was zero covid. Everyone should now contemplate how that would have been, who would have been most damaged by it, and who would have been fine.
Spot on as usual @mendel_random - but no-one but govt policy makers were not listening.
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The most highly cited gene-environment interactions in psychiatric epidemiology (and perhaps in the field overall), one of which was Science paper of the year for 2002, are spurious. Plenty of lessons to be learnt here.
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Is anyone else feeling enormously cheered up by the fact their twitter feed is becoming less and less covid-centric?.
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This letter in @bmj_latest from two people who’ve spent their careers researching vaccines deserves to be read
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In "Noodles, no nulls and numb skulls: threats to the future of Mendelian randomization" I discuss the triple threats of nonsense papers, methods no one understands that produce obviously spurious findings, & why MR studies now all have positive results
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Like many I’ve hoped that the observational epidemiological associations suggesting alcohol protected against cardiovascular disease (CVD) were true. Unfortunately, this is not the case, a paper by Iona Millwood, Zhengming Chen, Richard Peto et al shows
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This short paper is worth reading slowly and carefully, at least twice. It is the best single explainer of the basic pattern of covid mortality by age in the UK, and if thought long and hard about will lead to many questions, as all good explanations should.
My BMJ paper on using the idea of ‘normal’/background/actuarial risk to communicate the huge range of risks from COVID-19 experienced by people of different ages
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1/n “lives vs economy” is unhelpful, it is not primarily the economy and jobs that are diminished by full or partial lockdowns, rather the almost unimaginable richness of life in all its domains suffers. We are social beings, and a major part of that sociality is stripped from us.
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Next time round can we please only listen to people who recognize that this was (1) clearly endemic from February 2020 (2) population/herd immunity refers to immunity levels that reduce the severity of illness in those infected, not protection from carriage of the virus.
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Hot air can be damaging to those you love - including if that person is you
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Very informative @jimalkhalili #TheLifeScientific with @neil_ferguson. A thread disputing his conclusion that we face "a trade off between saving lives and saving the economy and jobs". It is so much broader than that .
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There’s no such thing as “progressive nationalism”; there’s no such thing as “progressive border closures”; there’s no such thing as “socialism in one country”. They all lead to misery and xenophobia. Internationalism is the only progressive way to go.
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The trajectories of “epidemiologists”.who made their popular reputations during the pandemic will be interesting.
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Brilliant article on the notion that viral load at time of infection is a key determinant of clinical course, ending with this inspiring final paragraph on how clinical and population-based epidemiology should work together .
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A must-read for anyone interested in personalized medicine. Meaningful individual differences in response may be the exception not the norm
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In 1994 in Edinburgh HJ Eysenck presented his fraudulent “findings” on how a psychological therapy could basically abolish cancer. I said his own data showed what he said could not be true, and his response was not reassuring (At 1.16.35) . / cont.
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Unsurprisingly @MichaelMarmot has been at the forefront of those insisting we see the pandemic through the lens of inequality and inequity. Some more much deserved recognition
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Omicron is illustrating "herd immunity" as how it was introduced: a relative concept, that reduces the adverse outcome of infections within populations, not as an absolute threshold that stopped transmission; as @bmj_latest #covidunknowns webinar explains
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"In science, as against careerism or pure mathematics, it is better to be approximately correct and scientifically relevant than it is to be precisely correct but humanly irrelevant"
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Can we have an absolute moratorium on people who have a garden from issuing censorious statements regarding those who don’t have gardens using outdoor spaces (with appropriate physical distancing)? Please . .
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What excuse do you have for using the term "statistically significant" in 2017? @jonathanasterne on common answers
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Yet another example of when RCT and Mendelian randomization data triangulate to give a clear answer in an area where conventional naive observational epidemiology has delivered a mass of conflicting and confusing evidence. Viva triangulation!
It’s final: vitamin D does not reduce risk of depression or mood changes. Doctors at Harvard compared vitamin D with placebo in 18 000 people for 5 years, and found no effect. Earlier trials and Mendelian randomization studies also found no effect.
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A ludicrous comment - childhood obesity has a larger genetic component than educational performance, but the increase over time in childhood obesity shows how much it can be influenced by the environment. Heritability says little about what interventions could achieve.
If you scrapped private schools it wouldn't make as much difference as the Left thinks. That's because educational performance has high genetic component, meaning it can only be socially engineered so much. Private schools facilitate genetic potential better than state, that's it.
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Richard Peto, a scientist who changed the world, on @jimalkhalili on @BBCRadio4. Beautifully explains so many issues that health sciences get wrong, and the simple solutions to them
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🤔 both a single episode of natural infection and vaccination give life time protection against reinfection in measles. Covid is probably like other season coronaviruses and gives much shorter protection 🤔 so, erm, no . .
More thoughts out Mon AM but I see this more like measles than flu. A vaccine helps us move towards a measles model. Eliminated largely in rich countries with continual flare-ups requiring outbreak response; continual struggle in poor countries.
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For anyone who'd like to discuss the strengths and weaknesses of Mendelian randomization I will be doing so @broadinstitute in Boston on 12th May at 3pm Boston time / 8pm UK time in person and online, followed by a reception for those there in person
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Want to understand Mendelian randomization but only have 2 minutes? Try Got 5 minutes? Then Want 30 minutes? Here: Or a (working) lifetime? We are always hiring @mrc_ieu.
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"Inequality helped define the pandemic. It is likely to define even more the post-pandemic world. And it will do so because of deliberate “I’m all right, Jack” decisions taken by politicians in the rich world" Great piece on vaccine equity by @kenanmalik.
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Population SARs-CoV-2 screening only ethical if an intervention follows on from it; this only exists if there is full economic and social support for self-isolation. Spot-on @bmj_latest editorial by @mugecevik .@sdbaral Alex Crozier @jackiecassell
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For me at least a great discussion (with perfect chairing and participation from the audience) of #bookofwhy with @yudapearl @ucla Now just to get Judea to write more on Mendelian randomization . No bullet proof vests were required .
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A short thread for the myriad researchers cranking the handle on @uk_biobank COVID data. I am a UKB participant, I am pretty certain I was an early UK COVID case (worst winter sickness I've had, weird loss of taste and before that was noted as a symptom), however I will not . .
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There are still many aspects of covid-19 that are inadequately understood. Following the popular day-long "Covid-19: known unknowns" webinar @bmj_latest & @mrc_ieu will be running a series of 6 shorter webinars, the first on covid and schools on 28th Jan
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Some great personal news! The distribution of my annual income over the past 40 years looks pretty much like the blue data in the slide below, so I have applied the reliable model used here to project forwards, and I am going to me a multi-billionaire in a few years time 🥂
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A year ago this already seminal paper by Jennie Lavine and colleagues appeared in @ScienceMagazine on the transition of SARS-CoV-2 to endemicity. Sadly, some remain resistant to science & even now prefer unicorns
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Childhood vaccination - discuss with people who aren't ABSOLUTELY certain about ABSOUTELY everything @bmj_latest @mrc_ieu #CovidUnknowns webinar 9th Sept 4pm with @russellviner @sridhartweet @shamezladhani @adamhfinn @stabellBenn @ParsnipsParsons @fgodlee.
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Important paper on the often ignored issue of barriers to academic careers due to social background (and the more widely - but still too little - discussed issues of gender, ethnicity, sexual orientation, disability and age). A thread 👇
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preening self-appointed fear-mongers with limited (usually no) pre-covid expertise in the important scientific domains who have contributed absolutely nothing scientific and have poisoned the public sphere with their bluster, self-promotion and ignorance?.
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Awesome review of genetically informed epidemiological designs for strengthening causal inference - twin studies, Mendelian randomization & hybrid designs - for the novice and experienced practitioner alike. Kudos to @JBPingault Frank Dudbridge and co
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This cartoon blog by @EpiEllie about a great (short) book on causation is tremendous and orders its insights better than my brain could do when reading the book
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Progress of epidemics is uncertain. This is seen in tightly standardized epidemics in animal populations. No one is omniscient & getting things wrong is normal. Deleting tweets predicting a massive June peak acts against understanding Embrace being wrong!.
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Why has the proportion of cancers that could be prevented by known means not increased over 40 years? @Lyonpaul Bert Hofman & I suggest it could be that exposures are ubiquitous (a cancer-focused update plus Richard Peto homage)
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On personal crusade to correct every copy of @thetimes misleading alcohol in pregnancy story. Absence of evidence is NOT evidence of absence
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Epidemiologists: if you are *certain* something is true and were vocally campaigning to implement your favoured intervention before your research was conducted, you are unlikely to be an appropriate researcher to work on this issue, and publish it in leading clinical journals.
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I am talking (online, sadly but obvs) on “The Fundamental Principles of Mendelian Randomization” @HarvardChanSPH @HarvardEpi on 18th November 2020 at US Eastern time 1.00pm (UK time 6.00pm). Open to all.
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Rather than threaten the independence of the JCVI in such an unsubtle way @sajidjavid should register for the @bmj_latest @mrc_ieu "known unknowns" webinar on childhood vaccination 9th Sept 4pm UK time and hear some expert opinion emphasizing uncertainties
While we await final advice from the independent experts at the JCVI, I've asked the NHS to be ready to rollout vaccines to 12-15 yr olds. Read my piece on how we continue to build our wall of defence against this virus:
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Another utterly reliable output from the Ioannidis factory. From my listing I have been publishing papers since 1966 (when I was aged 7) . it seems not even basic checks are carried out with these searches.
Ioannidis et al created an open-access database of 100,000 top scientists. It provides information on citations, h-index etc.
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Guidelines for conducting Mendelian randomization studies, led by @stevesphd with @nm_davies, Frank Dudbridge, @dpsg108, @MariaGlymour, Fernando P. Hartwig, Cosetta Minelli, @mvholmes, @carolinerelton, Evropi Theodoratou. Comments welcome (for revisions).
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Fascinating and thought-provoking discussion on why there are so few circulating coronaviruses in humans, from the much longer list of potential ones, by Benjamin Rice et al .
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A survey of immunologists, virologists & infectious disease researchers by @nature of likely covid-19 futures. A clear majority for a different picture to that of the "beautiful dream" of #ZeroCovid Do media reports in the UK reflect this expert view? 🤔
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Principles of Evidence Based Medicine 2021 style: there is absolutely nothing to be learnt from RCTs if they happen to have got the wrong answer.
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A fascinating read on how the supposed "good guys" in the nutritional epidemiology field - those fighting valiantly to protect you from dying of eating red meat - game the system and defend their flawed methodology
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I have an epidemiology joke: nutritional epidemiology.
@MenonBioPhysics I have an epidemiology joke but you R0 going to get it.
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Actually he didn't. The real story is more interesting
English physician John Snow stopped a cholera outbreak in Soho,London on September 08,1854. He is one of the fathers of modern epidemiology.
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Most inspiring @BBCRadio4 #TheLifeScientific ever? @Dr_Black on leaving school at 16, single mum, 3 small kids and university at 26, saying yes to doing a PhD when not knowing what one was, saving @bletchleypark & more.@jimalkhalili -
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As clear an answer as can currently be given to the question of how much of the ‘normal’ risk of death does Covid represent? by @d_spiegel
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“This pandemic has seen an unprecedented intergenerational transfer of harm and costs from elderly socioeconomically privileged people to disadvantaged children"
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Gr8 @EpiEllie “Sick individuals and sick populations” (SISP) a classic; along with his many other writings (including his valedictory book “Strategy of Preventive Medicine”) it should have remade the epidemiological landscape. A thread here on a few interpretive differences.
Next up, Sick Individuals and Sick Populations by Geoffrey Rose, 1985. We talked about his paper during this summer’s #epipeopleshealth #epibookclub but I’d never read it. It’s great & (at least from my reading) argues *for* well-defined causal questions
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That @Nature publishes something so scientifically illiterate is shocking. Herd immunity is a description of a biological process, it hasn't got "proponents". It is like saying "proponents of gravity". The editors need Thursday's @bmj_latest webinar/cont
Scientists: don’t feed the doubt machine
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Questions worth considering before making sweeping statements about herd immunity: (1) why do the seasonal coronaviruses circulate widely without making many people seriously ill? (2) if we had witnessed their initial introduction into humans would this have been benign? 🤔.
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7/7 One final lesson from this sad story: never think "liberal" authoritarians have any interest in what is in the interests of those less privileged than themselves, and make the mistake of confusing them with socialists.
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This 👇 UK also had massive connectivity and much higher early dissemination, the notion London could have been Canberra or Wellington makes no sense, the message we’ll hear that zero covid was possible but the UK’s complicity in the genesis of the Johnson (Delta) variant / cont.
The UK 🇬🇧 has had a rough pandemic, but our scientific community has given the world:. -Best therapeutics RCT (RECOVERY).-Only non-commercial vaccine RCT (Oxford vaccine).-Best real world vaccine effectiveness data (PHE/ONS).-Worlds only mass testing surveillance data (ONS). 1/2.
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Honoured to be elected a member of @EMBO as perhaps the only old-school shoe leather epidemiologist in its history? Makes the time spent working my way thru those basic college textbooks of molecular and population genetics 25 years ago worthwhile
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From the beginning the SARS-CoV-2 pandemic was not "a trade off between saving lives and saving the economy and jobs". It wasn't "lives versus the economy" it was "lives versus lives". A thread from a time when this was already clear.
1/n “lives vs economy” is unhelpful, it is not primarily the economy and jobs that are diminished by full or partial lockdowns, rather the almost unimaginable richness of life in all its domains suffers. We are social beings, and a major part of that sociality is stripped from us.
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Excellent @bmj_latest editorial by epidemiology legend Raj Bhopal & @apsmunro Covid is harming scholarly communication. They play it as it lays: "labelling different interpretations of evidence [by fellow academics] as 'disinformation' is inappropriate"
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50 years ago Richard Lewontin said it would take a cohort of 300-400,000 to demonstrate human evolution in action That number with genetic data did the job Lewontin wanted a birth cohort, though; we need a 500K Biobank-Junior.
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Home after 1st hip replaced @NorthBristolNHS Whole experience great: cleaners, nurses, porters, junior docs, radiographers, tea service, anaesthetics, admin; even the sawbones was great. I love the NHS & am so thankful we don't have a US-type system. Shame @jeremy_hunt disagrees.
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Clinical trials were born amid the chaos of the late 19th century plague epidemic in India. I'll be giving a virtual seminar on this at 4pm BST tomorrow 7th April (need to scroll down link for access details)
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Just replace "microbiome" with the fad of your choice for the previous "game-changer" which didn't . erm . change the game
How strategies to manipulate the microbiome could be game-changing in cancer treatment.
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& Mediterranean diet causes you to smoke less, be of higher social class, have higher IQ 60 years ago . amazing .
Older people who followed a Mediterranean diet retained more brain volume over three years @NeurologyToday
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Strange experience receiving a quarter century long service award @BristolUni Didn’t think I’d stay 5 let alone 25 years, but it’s a great city and has been a fantastic journey including @CO90s and @mrc_ieu However the shock has transformed @carolinerelton I’m not sure positively
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