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- Title
Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry: Bi-genomic dependence raises major concerns for link to disease.
- Authors
Hagen, Christian M.; Gonçalves, Vanessa F.; Hedley, Paula L.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Hansen, Christine S.; Kanters, Jørgen K.; Nielsen, Jimmi; Mors, Ole; Demur, Alfonso B.; Als, Thomas D.; Nordentoft, Merete; Børglum, Anders; Mortensen, Preben B.; Kennedy, James; Werge, Thomas M.; Hougaard, David M.; Christiansen, Michael
- Abstract
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.
- Subjects
SCHIZOPHRENIA; SINGLE nucleotide polymorphisms; GENEALOGY; STRATIGRAPHIC geology; MITOCHONDRIAL DNA
- Publication
PLoS ONE, 2018, Vol 13, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0208828