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

TitleSpatial fine-mapping for gene-by-environment effects identifies risk hot spots for schizophrenia.
Publication TypeJournal Article
Year of Publication2018
AuthorsFan CChieh, McGrath JJ, Appadurai V, Buil A, Gandal MJ, Schork AJ, Mortensen PBo, Agerbo E, Geschwind SA, Geschwind D, Werge T, Thompson WK, Pedersen CBøcker
JournalNat Commun
Date Published2018 12 13
KeywordsChromosome Mapping, Denmark, Environment, Genetic Predisposition to Disease, Geography, Humans, Proof of Concept Study, Risk Factors, Schizophrenia

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.

Alternate JournalNat Commun
PubMed ID30546018
PubMed Central IDPMC6294340
Grant ListR01 GM104400 / GM / NIGMS NIH HHS / United States
IRG Funded