Multi-PGS enhances polygenic prediction by combining 937 polygenic scores

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  • Clara Albiñana
  • Zhihong Zhu
  • Andrew J. Schork
  • Andrés Ingason
  • Hugues Aschard
  • Isabell Brikell
  • Cynthia M. Bulik
  • Liselotte V. Petersen
  • Esben Agerbo
  • Jakob Grove
  • Nordentoft, Merete
  • David M. Hougaard
  • Werge, Thomas
  • Anders D. Børglum
  • Preben Bo Mortensen
  • John J. McGrath
  • Benjamin M Neale
  • Florian Privé
  • Bjarni J. Vilhjálmsson

The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R 2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.

Original languageEnglish
Article number4702
JournalNature Communications
Volume14
Number of pages11
ISSN2041-1723
DOIs
Publication statusPublished - 2023

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