Evidence map›Paper›PMID 18038153›Full record

ReviewHuman genetics2008

Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology?

Shah Ebrahim, George Davey Smith

Abstract readReview
PubMed Publisher
In one paragraph

Review in Human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed, 7 pooled it
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

220 citing papers in PubMed, 7 syntheses or guidelines pooled it, 442 citations in OpenAlex.

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  9. Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2013
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  16. Redefining oropharyngeal cancer in the HPV era: integrating precision medicine and immunotherapeutic frontiers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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160 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Shah EbrahimNoncommunicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK. shah.ebrahim@lshtm.ac.uk
George Davey Smith
London School of Hygiene & Tropical Medicine · GBUniversity of Bristol · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Establishing causal relationships between environmental exposures and common diseases is beset with problems of unresolved confounding, reverse causation and selection bias that may result in spurious inferences. Mendelian randomization, in which a functional genetic variant acts as a proxy for an environmental exposure, provides a means of overcoming these problems as the inheritance of genetic variants is independent of-that is randomized with respect to-the inheritance of other traits, according to Mendel's law of independent assortment. Examples drawn from exposures and outcomes as diverse as milk and osteoporosis, alcohol and coronary heart disease, sheep dip and farm workers' compensation neurosis, folate and neural tube defects are used to illustrate the applications of Mendelian randomization approaches in assessing potential environmental causes of disease. As with all genetic epidemiology studies there are problems associated with the need for large sample sizes, the non-replication of findings, and the lack of relevant functional genetic variants. In addition to these problems, Mendelian randomization findings may be confounded by other genetic variants in linkage disequilibrium with the variant under study, or by population stratification. Furthermore, pleiotropy of effect of a genetic variant may result in null associations, as may canalisation of genetic effects. If correctly conducted and carefully interpreted, Mendelian randomization studies can provide useful evidence to support or reject causal hypotheses linking environmental exposures to common diseases.

Indexed as

Genome, HumanMolecular EpidemiologyGenetic Diseases, InbornHumansLinkage Disequilibrium

Identifiers

PMID18038153
OpenAlexW2116908385

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.