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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
A Comprehensive Analysis of Nuclear-Encoded Mitochondrial Genes in Schizophrenia
Biological Psychiatry, Volume 83, No. 9, Year 2018
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Description
Background: The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial dysfunction may play a role in SCZ, but comprehensive association studies are lacking. We hypothesized that variants in nuclear-encoded mitochondrial genes influence susceptibility to SCZ. Methods: We conducted gene-based and gene-set analyses using summary association results from the Psychiatric Genomics Consortium Schizophrenia Phase 2 (PGC-SCZ2) genome-wide association study comprising 35,476 cases and 46,839 control subjects. We applied the MAGMA method to three sets of nuclear-encoded mitochondrial genes: oxidative phosphorylation genes, other nuclear-encoded mitochondrial genes, and genes involved in nucleus-mitochondria crosstalk. Furthermore, we conducted a replication study using the iPSYCH SCZ sample of 2290 cases and 21,621 control subjects. Results: In the PGC-SCZ2 sample, 1186 mitochondrial genes were analyzed, among which 159 had p values <.05 and 19 remained significant after multiple testing correction. A meta-analysis of 818 genes combining the PGC-SCZ2 and iPSYCH samples resulted in 104 nominally significant and nine significant genes, suggesting a polygenic model for the nuclear-encoded mitochondrial genes. Gene-set analysis, however, did not show significant results. In an in silico protein-protein interaction network analysis, 14 mitochondrial genes interacted directly with 158 SCZ risk genes identified in PGC-SCZ2 (permutation p =.02), and aldosterone signaling in epithelial cells and mitochondrial dysfunction pathways appeared to be overrepresented in this network of mitochondrial and SCZ risk genes. Conclusions: This study provides evidence that specific aspects of mitochondrial function may play a role in SCZ, but we did not observe its broad involvement even using a large sample. © 2018 Society of Biological Psychiatry
Authors & Co-Authors
Cappi, Carolina
Brazil, Sao Paulo
Universidade de São Paulo
Hagen, Christian Munch
Denmark, Copenhagen
Statens Serum Institut
Derkach, Andriy
Canada, Toronto
University of Toronto
Zai, Clement C.
Canada, Toronto
University of Toronto
Canada, Toronto
Centre for Addiction and Mental Health
Hedley, P. L.
Denmark, Copenhagen
Statens Serum Institut
Bybjerg-Grauholm, Jonas
Denmark, Copenhagen
Statens Serum Institut
Sullivan, Patrick F.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Sweden, Stockholm
Karolinska Institutet
Christiansen, Michael
Denmark, Copenhagen
Statens Serum Institut
Denmark, Copenhagen
Københavns Universitet
Kennedy, James Lowery
Canada, Toronto
University of Toronto
Canada, Toronto
Centre for Addiction and Mental Health
Statistics
Citations: 30
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1016/j.biopsych.2018.02.1175
ISSN:
00063223
Research Areas
Cancer
Genetics And Genomics
Mental Health
Study Approach
Systematic review