Lars Henrik Fugger

Identifying cross-disease components of genetic risk across hospital data in the UK Biobank

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Adrian Cortes, University of Oxford, Oxford
  • ,
  • Patrick K Albers, University of Oxford, Oxford
  • ,
  • Calliope A Dendrou, University of Oxford, Oxford
  • ,
  • Lars Fugger
  • Gil McVean, University of Oxford, Oxford

Genetic risk factors frequently affect multiple common human diseases, providing insight into shared pathophysiological pathways and opportunities for therapeutic development. However, systematic identification of genetic profiles of disease risk is limited by the availability of both comprehensive clinical data on population-scale cohorts and the lack of suitable statistical methodology that can handle the scale of and differential power inherent in multi-phenotype data. Here, we develop a disease-agnostic approach to cluster the genetic risk profiles for 3,025 genome-wide independent loci across 19,155 disease classification codes from 320,644 participants in the UK Biobank, representing a large and heterogeneous population. We identify 339 distinct disease association profiles and use multiple approaches to link clusters to the underlying biological pathways. We show how clusters can decompose the variance and covariance in risk for disease, thereby identifying underlying biological processes and their impact. We demonstrate the use of clusters in defining disease relationships and their potential in informing therapeutic strategies.

Original languageEnglish
JournalNature Genetics
Pages (from-to)126-134
Number of pages9
Publication statusPublished - Dec 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Copyright 2020 Elsevier B.V., All rights reserved.

    Research areas

  • Adult, Aged, Biological Specimen Banks, Female, Gene-Environment Interaction, Genetic Diseases, Inborn/genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Quantitative Trait, Heritable, Risk Factors, United Kingdom, PATHWAYS, SUSCEPTIBILITY LOCI, MUTATIONS, TRAITS, GENOME-WIDE ASSOCIATION, VARIANTS, THROMBOSIS, IDENTIFICATION, SELECTION, INSIGHTS

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