PT  - JOURNAL ARTICLE
AU  - Christian M Hagen
AU  - Vanessa F Gonçalves
AU  - Paula L Hedley
AU  - Jonas Bybjerg-Grauholm
AU  - Marie Bækvad-Hansen
AU  - Christine S Hansen
AU  - Jørgen K Kanters
AU  - Jimmi Nielsen
AU  - Ole Mors
AU  - Alfonso B Demur
AU  - Thomas D Als
AU  - Merete Nordentoft
AU  - Anders Børglum
AU  - Preben Bo Mortensen
AU  - James Kennedy
AU  - Thomas M Werge
AU  - David M Hougaard
AU  - Michael Christiansen
TI  - 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
AID  - 10.1101/149070
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 149070
4099  - http://biorxiv.org/content/early/2017/06/12/149070.short
4100  - http://biorxiv.org/content/early/2017/06/12/149070.full
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.