Stephen Burgess@stevesphd

Medical statistician, work with genetic data to disentangle causation from correlation. Author of book on Mendelian randomization.

 Cambridge, England
mendelianrandomization.com/
Joined May 2010
155 Photos and videos
Guidelines on performing Mendelian randomization investigations written by an all-star line-up of MR researchers are now available on Wellcome Open Research: wellcomeopenresearch.org/art… - represents a consensus statement after 12+ months of deliberation. Comments welcome!
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New publication "What phases of the drug development framework can epidemiological studies emulate?" at Am J Epi led by me (!), with contributions from @ja_labrecque_, @BarWoolf, Emily, David R, and Sofia: academic.oup.com/aje/advance…

What phases of the drug development framework can epidemiological studies emulate?

Abstract. Target trial emulation prompts investigators to frame their analysis question in terms of a hypothetical clinical trial. Although this does not s

academic.oup.com
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We encourage a broader framing of target trial emulation: alongside “estimand first” approaches, we should consider “design first” or “assumption first” approaches - where we start by asking "What quantity can we estimate reliably?".
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In doing this, we may get a more valid estimate of a less relevant quantity, rather than a less valid estimate of a more relevant quantity. In many cases, the estimand is a good servant, but a poor master.
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New paper "Causal inference in Clinical Research: A Primer" at Journal of Periodontal Research - pubmed.ncbi.nlm.nih.gov/4246… led by Nasir Bashir plus co-authors Moritz Kebschull and Gustavo Nascimento.
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I think he agrees with me now that this was a touch ambitious, but the result is 19 pages that spans from asking questions to parameter identification (covering adjustment-based and design-based approaches) to analysis and beyond.
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Many of the examples relate to dentistry, but the principles are universal: the credibility of a causal claim is determined not primarily by the statistical method, but by whether the underlying assumptions are considered plausible within the context of the scientific question.
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Stephen Burgess retweeted
Guoyi Yang@yanggy_hku
Jul 13
Our study provides genetic evidence that GLP-1R activation is associated with better mental health well-being, lower risk of depression, and lower risk of bipolar disorder, possibly beyond its effect on BMI and HbA1c. Online at Translational Psychiatry: nature.com/articles/s41398-0…

Glucagon-like peptide-1 receptor activation and mental health: a drug-target mendelian randomizat...

Translational Psychiatry - Glucagon-like peptide-1 receptor activation and mental health: a drug-target mendelian randomization study

nature.com
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New paper: Blood Manganese and Risk of Squamous Cell Carcinomas of the Head and Neck published in JAMA Otolaryngology @JAMAOto led by Benjamin Clay and Paul Carter, together with Nasir Bashir: jamanetwork.com/journals/jam….

Blood Manganese and Risk of Squamous Cell Carcinomas of the Head and Neck

This cis-mendelian randomization study aims to determine if variations in genetically predicted blood manganese are associated with risk of squamous cell carcinomas of the oral cavity, oropharynx,...

jamanetwork.com
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We tested whether these variants associated with different head and neck cancers. We saw positive associations for all cancer types, with significant estimates for oral cavity squamous cell carcinoma (OCSCC) and HPV-positive oropharynx squamous cell carcinoma (OPSCC).
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Several limitations as ever, but great to see supportive evidence from human genetics for a biologically-plausible mechanism. Learnings for me about heterogeneity in oral cancers: different parts of the oral cavity get cancer via distinct mechanisms. Comments welcome!
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New publication "Comparison of methods for assessing effects of risk factors on disease progression in Mendelian randomization under index event bias" at @AJHGNews: authors.elsevier.com/sd/arti…. Collaboration between Eli Lilly, Sequoia Genetics, and Cambridge University. Brief thread:
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...and 4) if none of these approaches are possible, perform a naive analysis and estimate the likely magnitude of bias that could occur under realistically severe index event bias.
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Thanks to Linxuan Zhang for leading the work, all those at Lilly for their valuable input (particularly Zae, Yushi, and Pallav), and @dpsg108 at Sequoia for bringing everything together. Comments and questions are always welcome!
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