Evidence map›Paper›PMID 28968646›Full record

ArticleBiostatistics (Oxford, England)2018

PolyGEE: a generalized estimating equation approach to the efficient and robust estimation of polygenic effects in large-scale association studies.

Julian Hecker, Dmitry Prokopenko, Christoph Lange, Heide Loehlein Fier

Open access · hybridAbstract read
In one paragraph

Article in Biostatistics (Oxford, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 18% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Controlling for polygenic genetic confounding in epidemiologic association studies.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Article
  4. 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

4 authors at 2 institutions in 2 countries.

Julian HeckerDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA and Department of Genomic Mathematics, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
Dmitry ProkopenkoChanning Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Christoph LangeDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA and Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Heide Loehlein FierDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA and Department of Genomic Mathematics, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
Brigham and Women's Hospital · USUniversity of Bonn · DE

Funding

Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L · 2016 to 2020
$12.6M
Physics of collective cellular migration in lung health and diseaseP01HL120839 · NHLBI · HARVARD SCHOOL OF PUBLIC HEALTH · PI FREDBERG, JEFFREY J · 2014 to 2018
$12.2M
A New Approach to Mental Health Phenotypes in Family Genomewide AssociationR01MH087590 · NIMH · HARVARD SCHOOL OF PUBLIC HEALTH · PI LANGE, CHRISTOPH · 2010 to 2013
$1.6M
Preparing Association Analysis Software Tools for Next Generation Sequencing DataR01HG008976 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LANGE, CHRISTOPH · 2016 to 2018
$1.1M
NHGRI NIH HHS R01 HG008976NHLBI NIH HHS P01 HL120839NHLBI NIH HHS P01 HL132825NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897NIMH NIH HHS R01 MH087590
6 · The paper itself

Abstract

To quantify polygenic effects, i.e. undetected genetic effects, in large-scale association studies, we propose a generalized estimating equation (GEE) based estimation framework. We develop a marginal model for single-variant association test statistics of complex diseases that generalizes existing approaches such as LD Score regression and that is applicable to population-based designs, to family-based designs or to arbitrary combinations of both. We extend the standard GEE approach so that the parameters of the proposed marginal model can be estimated based on working-correlation/linkage-disequilibrium (LD) matrices from external reference panels. Our method achieves substantial efficiency gains over standard approaches, while it is robust against misspecification of the LD structure, i.e. the LD structure of the reference panel can differ substantially from the true LD structure in the study population. In simulation studies and in applications to population-based and family-based studies, we illustrate the features of the proposed GEE framework. Our results suggest that our approach can be up to 100% more efficient than existing methodology.

Indexed as

Linkage DisequilibriumModels, StatisticalBiostatisticsComputer SimulationGenome-Wide Association StudyHumansMental DisordersRegression Analysis

Identifiers

PMID28968646
PMCPMC5991211
OpenAlexW2807532129

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.