Department of Economics and Business Economics

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

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

  • Chun Chieh Fan, Mental Health Center Sct. Hans, Capital Region of Denmark, Roskilde, 4000, Denmark.
  • ,
  • John J McGrath
  • Vivek Appadurai, The Department of Biomedicine, Human Genetics, and Centre for Integrative Sequencing, iSEQ, Aarhus University, the The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, and the Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
  • ,
  • Alfonso Buil, The Department of Biomedicine, Human Genetics, and Centre for Integrative Sequencing, iSEQ, Aarhus University, the The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, and the Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
  • ,
  • Michael J Gandal, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA.
  • ,
  • Andrew J Schork, The Department of Biomedicine, Human Genetics, and Centre for Integrative Sequencing, iSEQ, Aarhus University, the The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, and the Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
  • ,
  • Preben Bo Mortensen
  • Esben Agerbo
  • Sandy A Geschwind, Scientific Decision Consulting, Santa Monica, CA, 90401, USA.
  • ,
  • Daniel Geschwind, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
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  • Thomas Werge, Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, DK-4000, Denmark.
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  • Wesley K Thompson, Family Medicine and Public Health Division of Biostatistics, University of California, San Diego, CA, 92093, USA. wes.stat@gmail.com.
  • ,
  • Carsten Bøcker Pedersen

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.

Original languageEnglish
JournalNature Communications
Volume9
Issue1
Pages (from-to)5296
ISSN2041-1723
DOIs
Publication statusPublished - 13 Dec 2018

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