Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry: Bi-genomic dependence raises major concerns for link to disease

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  • Christian M. Hagen, Statens Serum Institut
  • ,
  • Vanessa F. Gonçalves, University of Toronto
  • ,
  • Paula L. Hedley, Statens Serum Institut
  • ,
  • Jonas Bybjerg-Grauholm, Statens Serum Institut
  • ,
  • Marie Bækvad-Hansen, Statens Serum Institut
  • ,
  • Christine S. Hansen, Statens Serum Institut
  • ,
  • Jørgen K. Kanters
  • Jimmi Nielsen, Aalborg University
  • ,
  • Ole Mors
  • Alfonso B. Demur, Mental Health Centre
  • ,
  • Thomas D. Als
  • Merete Nordentoft, Mental Health Centre
  • ,
  • Anders Børglum
  • Preben B. Mortensen
  • James Kennedy, University of Toronto
  • ,
  • Thomas M. Werge, Mental Health Centre
  • ,
  • David M. Hougaard, Statens Serum Institut
  • ,
  • Michael Christiansen, Statens Serum Institut, University of Copenhagen

Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. An analysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 Danes without a psychiatric diagnosis and 2,538 schizophrenia patients, revealed marked inter-allelic differences in mitochondrial haplogroup affiliation and nuclear ancestry. This bi-genomic dependence could entail population stratification. Only two mitochondrial SNPs, m.15043A and m.15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation and nuclear ancestry. The extensive bi-genomic dependence documented here is a major concern when interpreting historic, as well as designing future, mtDNA association studies.

Original languageEnglish
Article numbere0208828
Number of pages14
Publication statusPublished - Dec 2018

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