Evidence map›Paper›PMID 38806447›Full record

ArticleAmerican journal of epidemiology2024

Joint modeling of gene-environment correlations and interactions using polygenic risk scores in case-control studies.

Ziqiao Wang, Wen Shi, Raymond J Carroll, Nilanjan Chatterjee

Abstract read
In one paragraph

Article in American journal of epidemiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Methods for modeling gene-environment interplay using polygenic risk scores.Statistical applications in genetics and molecular biology · 2026
    Review
  3. Article
  4. Article
  5. Gene-environment interactions in human health.Nature reviews. Genetics · 2024
    Review
  6. Statistical methods for gene-environment interaction analysis.Wiley interdisciplinary reviews. Computational statistics
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Ziqiao WangDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States.
Wen ShiMcKusick-Nathans Institute, Department of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United States.
Raymond J CarrollDepartment of Statistics, Texas A&M University, College Station, TX 77843, United States.
Nilanjan ChatterjeeDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States.

Funding

ECHODAC (Environmental Influences on Child Health Outcomes Data Analysis Center)U24OD023382 · OD · JOHNS HOPKINS UNIVERSITY · PI Diane J Catellier, LISA P JACOBSON · 2016 to 2026
$148.4M
Enabling improved applicability and transferability of polygenic scores across populationsU01HG011719 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI Alicia Martin · 2021 to 2026
$5.5M
Robust Methods for Polygenic Analysis to Inform Disease Etiology and Enhance Risk PredictionR01HG010480 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI CHATTERJEE, NILANJAN · 2019 to 2023
$2.8M
Multifactoral breast cancer risk prediction accounting for ethnic and tumor diversityU01CA249866 · NCI · JOHNS HOPKINS UNIVERSITY · PI CHATTERJEE, NILANJAN · 2020 to 2023
$2.3M
Enhancing the Interpretability and Applicability of Polygenic Scores through Multi-Omics Integration and Analysis of Family-Based StudiesK99HG013674 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI WANG, ZIQIAO · 2024 to 2025
$164k
NCI NIH HHS U01 CA249866NHGRI NIH HHS K99 HG013674NHGRI NIH HHS R01 HG010480NHGRI NIH HHS U01 HG011719NIH HHS 1R01HG010480-01NIH HHS 1U24OD023382-01NIH HHS U24 OD023382
6 · The paper itself

Abstract

Polygenic risk scores (PRSs) are rapidly emerging as a way to measure disease risk by aggregating multiple genetic variants. Understanding the interplay of the PRS with environmental factors is critical for interpreting and applying PRSs in a wide variety of settings. We develop an efficient method for simultaneously modeling gene-environment correlations and interactions using the PRS in case-control studies. We use a logistic-normal regression modeling framework to specify the disease risk and PRS distribution in the underlying population and propose joint inference across the 2 models using the retrospective likelihood of the case-control data. Extensive simulation studies demonstrate the flexibility of the method in trading-off bias and efficiency for the estimation of various model parameters compared with standard logistic regression or a case-only analysis for gene-environment interactions, or a control-only analysis, for gene-environment correlations. Finally, using simulated case-control data sets within the UK Biobank study, we demonstrate the power of our method for its ability to recover results from the full prospective cohort for the detection of an interaction between long-term oral contraceptive use and the PRS on the risk of breast cancer. This method is computationally efficient and implemented in a user-friendly R package.

Indexed as

Gene-Environment InteractionMultifactorial InheritanceBreast NeoplasmsCase-Control StudiesComputer SimulationFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansLogistic ModelsModels, GeneticRisk Factorscase-only analysiscohort studiesgene-environment interplaypopulation stratificationretrospective likelihoodUK Biobank

Identifiers

PMID38806447
PMCPMC11458198

What OpenQuestion holds

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Registered trials

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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.