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PLoS One. 2018 Dec 10;13(12):e0208828. doi: 10.1371/journal.pone.0208828. eCollection 2018.

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

Author information

Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada.
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Aalborg Psychiatric Hospital, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Mental Health Centre, Sct Hans, Capital Region of Denmark, Denmark.
Institute of Medical Genetics, Aarhus University, Aarhus, Denmark.
Mental Health Centre, Capital Region of Denmark, Denmark.
Center for Register Research, Institute of Economics, Aarhus University, Aarhus, Denmark.


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.

Conflict of interest statement

The authors have declared that no competing interests exist.

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