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PLoS One. 2018 Jan 25;13(1):e0191153. doi: 10.1371/journal.pone.0191153. eCollection 2018.

Examining the role of common and rare mitochondrial variants in schizophrenia.

Author information

1
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
2
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
3
Department of Genetics, University of North Carolina, Chapel Hill, NC, United States of America.
4
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA, United States of America.
5
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
6
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States of America.
7
Department of Nutrition, University of North Carolina, Chapel Hill, NC, United States of America.
8
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
9
Division of Psychiatric Genomics, Department of Psychiatry, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
10
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
11
Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
12
Data Science Institute and Medical School, Lancaster University, Bailrigg, Lancaster, LA1 4YW, United Kingdom.

Abstract

Oxidative phosphorylation within mitochondria is the main source of aerobic energy for neuronal functioning, and the key genes are located in mitochondrial DNA. Deficits in oxidative phosphorylation functioning have been reported for schizophrenia, but efforts in the identification of genetic markers within the mitochondrial DNA that predispose to schizophrenia have been limited. We genotyped a set of mitochondrial SNPs using Illumina HumanExome arrays and tested for association in the Swedish schizophrenia sample (N> 10,000). We developed a novel approach for mitochondrial DNA imputation in order to increase the number of common SNPs available for association analysis. The most significant findings were for the mitochondrial SNPs C15452A (GRCh38.p10; rs527236209; p = 0.007; gene MT-CYB; defining haplogroup JT); A11251G (rs869096886; p = 0.007; gene MT-ND4; defining haplogroup JT), and T4216C (rs1599988; p = 0.008, gene MT-ND1, defining haplogroup R2'JT). We also conducted rare variant burden analyses and obtained a p-value of 0.007. For multimarker haplotypes analysis, the most significant finding was for the J group (OR: 0.86, p = 0.02). We conducted the largest association study of mitochondrial DNA variants and schizophrenia but did not find an association that survived multiple testing correction. Analysis of a larger sample is required and will allow a better understanding of the role of mitochondria in schizophrenia.

PMID:
29370225
PMCID:
PMC5784966
DOI:
10.1371/journal.pone.0191153
[Indexed for MEDLINE]
Free PMC Article

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