RT Journal Article
SR Electronic
T1 Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 149070
DO 10.1101/149070
A1 Christian M Hagen
A1 Vanessa F Gonçalves
A1 Paula L Hedley
A1 Jonas Bybjerg-Grauholm
A1 Marie Bækvad-Hansen
A1 Christine S Hansen
A1 Jørgen K Kanters
A1 Jimmi Nielsen
A1 Ole Mors
A1 Alfonso B Demur
A1 Thomas D Als
A1 Merete Nordentoft
A1 Anders Børglum
A1 Preben Bo Mortensen
A1 James Kennedy
A1 Thomas M Werge
A1 David M Hougaard
A1 Michael Christiansen
YR 2017
UL http://biorxiv.org/content/early/2017/06/12/149070.abstract
AB Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. A reanalysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 normal Danes and 2,538 schizophrenia patients, revealed marked inter-allelic differences in haplogroup affiliation and nuclear ancestry, genogeophraphic affinity (GGA). This bi-genomic linkage disequilibrium (2GLD) 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. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.