Open AccessNovel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder
Author(s) -
Anton Schulmann,
Euijung Ryu,
Vanessa F. Gonçalves,
Brandi Rollins,
Michael Christiansen,
Mark A. Frye,
Joanna M. Biernacka,
Marquis P. Vawter
Publication year - 2019
Publication title -
complex psychiatry
Language(s) - English
Resource type - Journals
eISSN - 2673-3005
pISSN - 2673-298X
DOI - 10.1159/000495658
Subject(s) - mitochondrial dna , genetics , bipolar disorder , biology , epistasis , nuclear gene , population stratification , gene , mitochondrion , single nucleotide polymorphism , genotype , neuroscience , cognition
Mitochondrial dysfunction has been associated with schizophrenia (SZ) and bipolar disorder (BD). This review examines recent publications and novel associations between mitochondrial genes and SZ and BD. Associations of nuclear-encoded mitochondrial variants with SZ were found using gene- and pathway-based approaches. Two control region mitochondrial DNA (mtDNA) SNPs, T16519C and T195C, both showed an association with SZ and BD. A review of 4 studies of A15218G located in the cytochrome B oxidase gene (CYTB, SZ = 11,311, control = 35,735) shows a moderate association with SZ ( p = 2.15E-03). Another mtDNA allele A12308G was nominally associated with psychosis in BD type I subjects and SZ. The first published study testing the epistatic interaction between nuclear-encoded and mitochondria-encoded genes demonstrated evidence for potential interactions between mtDNA and the nuclear genome for BD. A similar analysis for the risk of SZ revealed significant joint effects (34 nuclear-mitochondria SNP pairs with joint effect p ≤ 5E-07) and significant enrichment of projection neurons. The mitochondria-encoded gene CYTB was found in both the epistatic interactions for SZ and BD and the single SNP association of SZ. Future efforts considering population stratification and polygenic risk scores will test the role of mitochondrial variants in psychiatric disorders.