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Nat Commun. 2018 Dec 13;9(1):5296. doi: 10.1038/s41467-018-07708-7.

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

Fan CC1,2, McGrath JJ3,4,5, Appadurai V2,6, Buil A2,6, Gandal MJ7, Schork AJ2,6, Mortensen PB3,6,8, Agerbo E3,6,8, Geschwind SA9, Geschwind D7,10, Werge T2,6,11,12, Thompson WK13,14,15, Pedersen CB16,17,18,19.

Author information

1
Center for Human Development, University of California, San Diego, CA, 92093, USA.
2
Mental Health Center Sct. Hans, Capital Region of Denmark, Roskilde, 4000, Denmark.
3
National Centre for Register-based Research, Aarhus University, Aarhus, 8210, Denmark.
4
Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
5
Queensland Centre for Mental Health Research, Wacol, QLD, 4076, Australia.
6
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.
7
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA.
8
Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, 8210, Denmark.
9
Scientific Decision Consulting, Santa Monica, CA, 90401, USA.
10
Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
11
Department of Clinical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
12
Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, 4000, Denmark.
13
Mental Health Center Sct. Hans, Capital Region of Denmark, Roskilde, 4000, Denmark. wes.stat@gmail.com.
14
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. wes.stat@gmail.com.
15
Family Medicine and Public Health Division of Biostatistics, University of California, San Diego, CA, 92093, USA. wes.stat@gmail.com.
16
National Centre for Register-based Research, Aarhus University, Aarhus, 8210, Denmark. cbp@econ.au.dk.
17
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. cbp@econ.au.dk.
18
Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, 8210, Denmark. cbp@econ.au.dk.
19
Big data Centre for Environment and Health, Aarhus University, Aarhus, 8210, Denmark. cbp@econ.au.dk.

Abstract

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (nā€‰=ā€‰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.

PMID:
30546018
PMCID:
PMC6294340
DOI:
10.1038/s41467-018-07708-7
[Indexed for MEDLINE]
Free PMC Article

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