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Examining the role of common and rare mitochondrial variants in schizophrenia

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • Vanessa F Gonçalves
  • Stephanie N Giamberardino
  • James J Crowley
  • Marquis P Vawter
  • Richa Saxena
  • Cynthia M Bulik
  • Zeynep Yilmaz
  • Christina M Hultman
  • Pamela Sklar
  • James L Kennedy
  • Patrick F Sullivan
  • Jo Knight
Article numbere0191153
<mark>Journal publication date</mark>25/01/2018
<mark>Journal</mark>PLoS ONE
Issue number1
Publication StatusPublished
<mark>Original language</mark>English


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.