title: Mitochondrial DNA sequence data reveals association of haplogroup U with psychosis in bipolar disorder.
abstract: Converging genetic, postmortem gene-expression, cellular, and neuroimaging data implicate mitochondrial dysfunction in bipolar disorder. This study was conducted to investigate whether mitochondrial DNA (mtDNA) haplogroups and single nucleotide variants (SNVs) are associated with sub-phenotypes of bipolar disorder. MtDNA from 224 patients with Bipolar I disorder (BPI) was sequenced, and association of sequence variations with 3 sub-phenotypes (psychosis, rapid cycling, and adolescent illness onset) was evaluated. Gene-level tests were performed to evaluate overall burden of minor alleles for each phenotype. The haplogroup U was associated with a higher risk of psychosis. Secondary analyses of SNVs provided nominal evidence for association of psychosis with variants in the tRNA, ND4 and ND5 genes. The association of psychosis with ND4 (gene that encodes NADH dehydrogenase 4) was further supported by gene-level analysis. Preliminary analysis of mtDNA sequence data suggests a higher risk of psychosis with the U haplogroup and variation in the ND4 gene implicated in electron transport chain energy regulation. Further investigation of the functional consequences of this mtDNA variation is encouraged.
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. Electronic address: mfrye@mayo.edu.
authors: Mark A
authors: MA
authors: Frye
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Euijung
authors: E
authors: Ryu
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors: Malik
authors: M
authors: Nassan
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Gregory D
authors: GD
authors: Jenkins
authors: Department of Psychiatry & Pharmacology, University of Toronto, Toronto, ON, Canada.
authors: Ana C
authors: AC
authors: Andreazza
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Jared M
authors: JM
authors: Evans
authors: Lindner Center of HOPE, Mason, OH, USA.
authors: Susan L
authors: SL
authors: McElroy
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Devin
authors: D
authors: Oglesbee
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors: W Edward
authors: WE
authors: Highsmith
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Joanna M
authors: JM
authors: Biernacka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C098483:NADH dehydrogenase subunit 4; C481838:MT-ND5 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I
keywords: Bipolar disorder; Haplogroup; Mitochondrial DNA; Psychosis; Single nucleotide variants