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

Christian M. Hagen; Vanessa F. Gonçalves; Paula L. Hedley; Jonas Bybjerg-Grauholm; Marie Bækvad-Hansen; Christine S. Hansen; Jørgen K. Kanters; Jimmi Nielsen; Ole Mors; Alfonso B. Demur; Thomas D. Als; Merete Nordentoft; Anders Børglum; Preben B. Mortensen; James Kennedy; Thomas M. Werge; David M. Hougaard; Michael Christiansen

doi:10.1371/journal.pone.0208828

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

Christian M. Hagen, Vanessa F. Gonçalves, Paula L. Hedley, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Christine S. Hansen, Jørgen K. Kanters, Jimmi Nielsen, Ole Mors, Alfonso B. Demur, Thomas D. Als, Merete Nordentoft, Anders Børglum, Preben B. Mortensen, James Kennedy, Thomas M. Werge, David M. Hougaard, Michael Christiansen^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

11 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	e0208828
Tidsskrift	PLoS ONE
Vol/bind	13
Udgave nummer	12
Antal sider	14
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0208828
Status	Udgivet - 1 dec. 2018

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10.1371/journal.pone.0208828

journal.pone.0208828Forlagets udgivne version, 1,47 MB

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Citationsformater

Hagen, C. M., Gonçalves, V. F., Hedley, P. L., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Hansen, C. S., Kanters, J. K., Nielsen, J., Mors, O., Demur, A. B., Als, T. D., Nordentoft, M., Børglum, A., Mortensen, P. B., Kennedy, J., Werge, T. M., Hougaard, D. M., & Christiansen, M. (2018). Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry: Bi-genomic dependence raises major concerns for link to disease. PLoS ONE, 13(12), [e0208828]. https://doi.org/10.1371/journal.pone.0208828

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

I: PLoS ONE, Bind 13, Nr. 12, e0208828, 01.12.2018.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Hagen, CM, Gonçalves, VF, Hedley, PL, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Hansen, CS, Kanters, JK, Nielsen, J, Mors, O, Demur, AB, Als, TD, Nordentoft, M, Børglum, A, Mortensen, PB, Kennedy, J, Werge, TM, Hougaard, DM & Christiansen, M 2018, 'Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry: Bi-genomic dependence raises major concerns for link to disease', PLoS ONE, bind 13, nr. 12, e0208828. https://doi.org/10.1371/journal.pone.0208828

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. / Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry : Bi-genomic dependence raises major concerns for link to disease. I: PLoS ONE. 2018 ; Bind 13, Nr. 12.

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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.",

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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

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