MITOCHONDRIAL DNA SNPS ASSOCIATED WITH SCHIZOPHRENIA EXHIBIT HIGHLY VARIABLE INTER-ALLELIC HAPLOGROUP AFFILIATION AND NUCLEAR GENOGEOGRAPHIC AFFINITY: BI-GENOMIC LINKAGE DISEQUILIBRIUM RAISES MAJOR CONCERN FOR LINK TO DISEASE
2019
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
haplogroupaffiliation 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
haplogroupaffiliation. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.
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