Evidence map›Paper›PMID 26993061›Full record

ArticleBiostatistics (Oxford, England)2016

Accounting for selection and correlation in the analysis of two-stage genome-wide association studies.

David S Robertson, A Toby Prevost, Jack Bowden

Open access · hybridAbstract read
In one paragraph

Article in Biostatistics (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. The benefits of covariate adjustment for adaptive multi-arm designs.Statistical methods in medical research · 2022
    Article
  3. Article
  4. Conditionally unbiased estimation in the normal setting with unknown variances.Communications in statistics: theory and methods · 2019
    Article
  5. Article
  6. Article
  7. Article
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

3 authors at 2 institutions in 1 country.

David S RobertsonMRC Biostatistics Unit, IPH Forvie Site, Robinson Way, Cambridge CB2 0SR, UK david.robertson@mrc-bsu.cam.ac.uk.
A Toby PrevostImperial College London, 1st Floor, Stadium House, 68 Wood Lane, London W12 7RH, UK.
Jack BowdenMRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Bristol BS8 2BN, UK and MRC Biostatistics Unit, IPH Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
MRC Biostatistics Unit · GBImperial College London · GB

Funding

Medical Research Council G1001799Medical Research Council MC_EX_MR/L012286/1Medical Research Council MC_UP_1302/2Medical Research Council MC_UP_1302/3Medical Research Council MC_UU_00002/3Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/9Medical Research Council MR/N01104X/1Medical Research Council MR/N501906/1
6 · The paper itself

Abstract

The problem of selection bias has long been recognized in the analysis of two-stage trials, where promising candidates are selected in stage 1 for confirmatory analysis in stage 2. To efficiently correct for bias, uniformly minimum variance conditionally unbiased estimators (UMVCUEs) have been proposed for a wide variety of trial settings, but where the population parameter estimates are assumed to be independent. We relax this assumption and derive the UMVCUE in the multivariate normal setting with an arbitrary known covariance structure. One area of application is the estimation of odds ratios (ORs) when combining a genome-wide scan with a replication study. Our framework explicitly accounts for correlated single nucleotide polymorphisms, as might occur due to linkage disequilibrium. We illustrate our approach on the measurement of the association between 11 genetic variants and the risk of Crohn's disease, as reported in Parkes and others (2007. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Gen. 39: (7), 830-832.), and show that the estimated ORs can vary substantially if both selection and correlation are taken into account.

Indexed as

Polymorphism, Single NucleotideSelection BiasCrohn DiseaseGenome-Wide Association StudyHumansCorrelated outcomesGenome-wide scanSelection biasTwo-stage sampleUniformly minimum variance conditionally unbiased estimator

Identifiers

PMID26993061
PMCPMC5031943
OpenAlexW2298564715

What OpenQuestion 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 OpenQuestion graph.