TY - JOUR
T1 - Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry
T2 - Bi-genomic dependence raises major concerns for link to disease
AU - Hagen, Christian M.
AU - Gonçalves, Vanessa F.
AU - Hedley, Paula L.
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Hansen, Christine S.
AU - Kanters, Jørgen K.
AU - Nielsen, Jimmi
AU - Mors, Ole
AU - Demur, Alfonso B.
AU - Als, Thomas D.
AU - Nordentoft, Merete
AU - Børglum, Anders
AU - Mortensen, Preben B.
AU - Kennedy, James
AU - Werge, Thomas M.
AU - Hougaard, David M.
AU - Christiansen, Michael
N1 - Publisher Copyright:
© 2018 Hagen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85058236229&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0208828
DO - 10.1371/journal.pone.0208828
M3 - Article
C2 - 30532134
AN - SCOPUS:85058236229
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0208828
ER -