Evidence map›Paper›PMID 30952951›Full record

ArticleNature communications2019

Adjustment for index event bias in genome-wide association studies of subsequent events.

Frank Dudbridge, Richard J Allen, Nuala A Sheehan, A Floriaan Schmidt, James C Lee, R Gisli Jenkins, Louise V Wain, Aroon D Hingorani, Riyaz S Patel

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 9 pooled it
–field-weighted citation impact
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

70 citing papers in PubMed, 9 syntheses or guidelines pooled it.

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  5. AAmerican journal of respiratory and critical care medicine · 2022
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  10. Article
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  14. Age-dependent Genetic Risk in Pulmonary Fibrosis Patients and Relatives.medRxiv : the preprint server for health sciences · 2026
    Article
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10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Frank DudbridgeDepartment of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK. frank.dudbridge@leicester.ac.uk.
Richard J AllenDepartment of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.ORCID http://orcid.org/0000-0002-8450-3056
Nuala A SheehanDepartment of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
A Floriaan SchmidtGroningen Research Institute of Pharmacy, University of Groningen, Groningen, 9700 AB, Netherlands.
James C LeeDepartment of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0SP, UK.ORCID http://orcid.org/0000-0001-5711-9385
R Gisli JenkinsNational Institute for Health Research, Nottingham Respiratory Biomedical Research Centre, City Campus, Nottingham, NG7 2RD, UK.ORCID http://orcid.org/0000-0002-7929-2119
Louise V WainDepartment of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.ORCID http://orcid.org/0000-0003-4951-1867
Aroon D HingoraniInstitute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, WC1E 6BT, UK.ORCID http://orcid.org/0000-0001-8365-0081
Riyaz S PatelInstitute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, WC1E 6BT, UK.

Funding

British Heart Foundation RG/10/12/28456Medical Research Council MR/N005953/1
6 · The paper itself

Abstract

Following numerous genome-wide association studies of disease susceptibility, there is increasing interest in genetic associations with prognosis, survival or other subsequent events. Such associations are vulnerable to index event bias, by which selection of subjects according to disease status creates biased associations if common causes of incidence and prognosis are not accounted for. We propose an adjustment for index event bias using the residuals from the regression of genetic effects on prognosis on genetic effects on incidence. Our approach eliminates this bias when direct genetic effects on incidence and prognosis are independent, and otherwise reduces bias in realistic situations. In a study of idiopathic pulmonary fibrosis, we reverse a paradoxical association of the strong susceptibility gene MUC5B with increased survival, suggesting instead a significant association with decreased survival. In re-analysis of a study of Crohn's disease prognosis, four regions remain associated at genome-wide significance but with increased standard errors.

Indexed as

Genome-Wide Association StudyModels, GeneticComputer SimulationCrohn DiseaseGenetic Predisposition to DiseaseHumansIdiopathic Pulmonary FibrosisIncidenceMucin-5BOdds RatioPolymorphism, Single NucleotideRegression AnalysisMUC5B protein, humanMucin-5B

Identifiers

PMID30952951
PMCPMC6450903

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.