Evidence map›Paper›PMID 23873611›Full record

ArticleGenetic epidemiology2013

Finding novel genes by testing G × E interactions in a genome-wide association study.

W James Gauderman, Pingye Zhang, John L Morrison, Juan Pablo Lewinger

Abstract read
In one paragraph

Article in Genetic epidemiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 5 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

81 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Gene-environment interactions in human health.Nature reviews. Genetics · 2024
    Review
  16. Article
  17. Article
  18. Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024
    Article
  19. Article
  20. Genome-wide interaction analysis of folate for colorectal cancer risk.The American journal of clinical nutrition · 2023
    Article

21 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

4 authors.

W James GaudermanDepartment of Preventive Medicine, University of Southern California, Los Angeles, California 90089, USA. jimg@usc.edu
Pingye Zhang
John L Morrison
Juan Pablo Lewinger

Funding

Translational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Joseph Leo Wiemels · 1996 to 2026
$46.4M
The EVE Asthma Genetics Consortium: Building Upon GWASRC2HL101651 · NHLBI · UNIVERSITY OF CHICAGO · PI NICOLAE, DAN LIVIU, OBER, CAROLE · 2009 to 2010
$7.4M
A Genome-wide Association Study of Childhood Respiratory OutcomesR01HL087680 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAUDERMAN, WILLIAM JAMES · 2007 to 2009
$4.1M
FLEXIBLE MULTI-LEVEL MODELS FOR LONGITUDINAL ANALYSIS OF CHILDHOOD OBESITYU01HD061968 · NICHD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BERHANE, KIROS T · 2009 to 2010
$795k
Detecting GxE Interactions in Genome-wide Association StudiesR21HL115606 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAUDERMAN, WILLIAM JAMES · 2012 to 2014
$481k
Design and Analysis of 2 Stage GWAS Study Using Next Generation Sequence TechnoloU01HG005927 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MARJORAM, PAUL · 2010 to 2010
$225k
Software to compute sample size for high-volume genetic studiesR41CA141852 · NCI · SUMMIT STATISTICS · PI GAUDERMAN, WILLIAM JAMES · 2009 to 2009
$116k
NCI NIH HHS R41 CA141852NCI NIH HHS R41CA141852NHGRI NIH HHS U01 HG005927NHGRI NIH HHS U01HG005927NHLBI NIH HHS 1RC2HL101651NHLBI NIH HHS R01 HL087680NHLBI NIH HHS R01HL087680NHLBI NIH HHS R21 HL115606NHLBI NIH HHS R21HL115606NHLBI NIH HHS RC2 HL101651NICHD NIH HHS U01 HD061968NICHD NIH HHS UO1HD061968NIEHS NIH HHS P30 ES007048NIEHS NIH HHS P30ES007048
6 · The paper itself

Abstract

In a genome-wide association study (GWAS), investigators typically focus their primary analysis on the direct (marginal) associations of each single nucleotide polymorphism (SNP) with the trait. Some SNPs that are truly associated with the trait may not be identified in this scan if they have a weak marginal effect and thus low power to be detected. However, these SNPs may be quite important in subgroups of the population defined by an environmental or personal factor, and may be detectable if such a factor is carefully considered in a gene-environment (G × E) interaction analysis. We address the question "Using a genome wide interaction scan (GWIS), can we find new genes that were not found in the primary GWAS scan?" We review commonly used approaches for conducting a GWIS in case-control studies, and propose a new two-step screening and testing method (EDG×E) that is optimized to find genes with a weak marginal effect. We simulate several scenarios in which our two-step method provides 70-80% power to detect a disease locus while a marginal scan provides less than 5% power. We also provide simulations demonstrating that the EDG×E method outperforms other GWIS approaches (including case only and previously proposed two-step methods) for finding genes with a weak marginal effect. Application of this method to a G × Sex scan for childhood asthma reveals two potentially interesting SNPs that were not identified in the marginal-association scan. We distribute a new software program (G×Escan, available at http://biostats.usc.edu/software) that implements this new method as well as several other GWIS approaches.

Indexed as

Gene-Environment InteractionModels, GeneticPolymorphism, Single NucleotideAsthmaCaliforniaCase-Control StudiesChild, PreschoolComputer SimulationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleSoftwareenvironmental factorGenome-wide scanpower

Identifiers

PMID23873611
PMCPMC4348012

What OpenQuestion holds

Textmetadata
LicenceTDM
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.