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Mendel’s laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues
Open accessAbstract
We respond to criticisms of Mendelian randomization (MR) by Mukamal, Stampfer and Rimm (MSR). MSR consider that MR is receiving too much attention and should be renamed. We explain how MR links to Mendel’s laws, the origin of the name and our lack of concern regarding nomenclature. We address MSR’s substantive points regarding MR of alcohol and cardiovascular disease, an issue on which they dispute the MR findings. We demonstrate that their strictures with respect to population stratification, confounding, weak instrument bias, pleiotropy and confounding have been addressed, and summarise how the field has advanced in relation to the issues they raise. We agree with MSR that “the hard problem of conducting high-quality, reproducible epidemiology” should be addressed by epidemiologists. However we see more evidence of confrontation of this issue within MR, as opposed to conventional observational epidemiology, within which the same methods that have demonstrably failed in the past are simply rolled out into new areas, leaving their previous failures unexamined.
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Metadata
- Authors
- Davey Smith, G., Holmes, M. V., Davies, N. M., & Ebrahim, S.
- Affiliations
- University of Oxford (GB)
- University of Bristol (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Venue
- European Journal of Epidemiology
- Published
- 2020-02
- Volume
- 35
- Issue
- 2
- Pages
- 99-111
- ISSN
- 0393-2990 (ISSN-L)
- 1573-7284
- PMC
- PMC7125255
- OpenAlex
- W3012912937
- Cited by
- 287
- References
- 118
- Citations by year
- 2026: 19 · 2025: 44 · 2024: 112 · 2023: 36 · 2022: 37 · 2021: 30 · 2020: 8
- FWCI
- 16.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Epidemiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (acceptedVersion, cc-by)
- Funders
- Medical Research Council (MC_UU_00011/1)
- British Heart Foundation (FS/18/23/33512)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- Mendelian randomization, Mendel's laws, causal inference, observational data, nomenclature, alcohol consumption, cardiovascular disease, population stratification, confounding, weak instrument bias, pleiotropy
- MeSH terms
- Cardiovascular Diseases, Humans, Genetic Variation, Molecular Epidemiology, Mendelian Randomization Analysis, Genetic Pleiotropy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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