Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction.

Case-Control Studies Disease / genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Models, Statistical Multifactorial Inheritance Phenotype Polymorphism, Single Nucleotide
PRS complex traits genetic prediction meta-analysis polygenic risk scores psychiatric disorders

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
03 06 2021
Historique:
received: 04 01 2021
accepted: 20 04 2021
pubmed: 9 5 2021
medline: 29 6 2021
entrez: 8 5 2021
Statut: ppublish

Résumé

The accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training sample size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWASs). However, it is now common for researchers to have access to large individual-level data as well, such as the UK Biobank data. To the best of our knowledge, it has not yet been explored how best to combine both types of data (summary statistics and individual-level data) to optimize polygenic prediction. The most widely used approach to combine data is the meta-analysis of GWAS summary statistics (meta-GWAS), but we show that it does not always provide the most accurate PRS. Through simulations and using 12 real case-control and quantitative traits from both iPSYCH and UK Biobank along with external GWAS summary statistics, we compare meta-GWAS with two alternative data-combining approaches, stacked clumping and thresholding (SCT) and meta-PRS. We find that, when large individual-level data are available, the linear combination of PRSs (meta-PRS) is both a simple alternative to meta-GWAS and often more accurate.

Identifiants

DOI: 10.1016/j.ajhg.2021.04.014 PMID: 33964208 PMC: PMC8206385
pubmed: 33964208
pii: S0002-9297(21)00145-2
doi: 10.1016/j.ajhg.2021.04.014
pmc: PMC8206385
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1001-1011

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Clara Albiñana (C)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark. Electronic address: albinanaclara@gmail.com.

Jakob Grove (J)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; Department of Biomedicine and Center for Integrative Sequencing, iSEQ, Aarhus University, 8000 Aarhus C, Denmark; Center for Genomics and Personalized Medicine, CGPM, Aarhus University, 8000 Aarhus C, Denmark; Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C, Denmark.

John J McGrath (JJ)

National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, QLD 4076, Australia; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.

Esben Agerbo (E)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark.

Naomi R Wray (NR)

Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.

Cynthia M Bulik (CM)

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.

Merete Nordentoft (M)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; Copenhagen University Hospital, Mental Health Centre Copenhagen Mental Health Services in the Capital Region of Denmark, 2100 Copenhagen Ø, Denmark; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, Denmark.

David M Hougaard (DM)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen S, Denmark.

Thomas Werge (T)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, 4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen N, Denmark; Lundbeck Foundation GeoGenetics Centre, GLOBE Institute, University of Copenhagen, 1350 Copenhagen K, Denmark.

Anders D Børglum (AD)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; Department of Biomedicine and Center for Integrative Sequencing, iSEQ, Aarhus University, 8000 Aarhus C, Denmark; Center for Genomics and Personalized Medicine, CGPM, Aarhus University, 8000 Aarhus C, Denmark.

Preben Bo Mortensen (PB)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark.

Florian Privé (F)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark.

Bjarni J Vilhjálmsson (BJ)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark; Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C, Denmark. Electronic address: bjv@econ.au.dk.

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questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Leveraging both individual-level genetic data...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Maladie › Leveraging both individual-level genetic data...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Leveraging both individual-level genetic data...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Leveraging both individual-level genetic data...
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questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Leveraging both individual-level genetic data...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Leveraging both individual-level genetic data...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Leveraging both individual-level genetic data...