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Spatial fine-mapping for gene-by-environment effects identifies risk hot spots for schizophrenia

Author

Listed:
  • Chun Chieh Fan

    (University of California
    Capital Region of Denmark)

  • John J. McGrath

    (Aarhus University
    University of Queensland
    Queensland Centre for Mental Health Research)

  • Vivek Appadurai

    (Capital Region of Denmark
    iPSYCH)

  • Alfonso Buil

    (Capital Region of Denmark
    iPSYCH)

  • Michael J. Gandal

    (University of California)

  • Andrew J. Schork

    (Capital Region of Denmark
    iPSYCH)

  • Preben Bo Mortensen

    (Aarhus University
    iPSYCH
    Aarhus University)

  • Esben Agerbo

    (Aarhus University
    iPSYCH
    Aarhus University)

  • Sandy A. Geschwind

    (Scientific Decision Consulting)

  • Daniel Geschwind

    (University of California
    University of California)

  • Thomas Werge

    (Capital Region of Denmark
    iPSYCH
    University of Copenhagen
    Mental Health Services of Copenhagen)

  • Wesley K. Thompson

    (Capital Region of Denmark
    iPSYCH
    University of California)

  • Carsten Bøcker Pedersen

    (Aarhus University
    iPSYCH
    Aarhus University
    Aarhus University)

Abstract

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.

Suggested Citation

  • Chun Chieh Fan & John J. McGrath & Vivek Appadurai & Alfonso Buil & Michael J. Gandal & Andrew J. Schork & Preben Bo Mortensen & Esben Agerbo & Sandy A. Geschwind & Daniel Geschwind & Thomas Werge & W, 2018. "Spatial fine-mapping for gene-by-environment effects identifies risk hot spots for schizophrenia," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07708-7
    DOI: 10.1038/s41467-018-07708-7
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