- Haplotypes and haplogroups are linked sets of common DNA variants, acting as susceptibility or protective factors to complex disorders. Growing evidence suggests that dysfunction of mitochondrial bioenergetics contributes to the schizophrenia phenotype. We studied mitochondrial DNA haplogroups in schizophrenia patients. Since mitochondria are inherited from the mothers, we used healthy fathers as an ideal case-control group. Analysis of the distribution of mitochondrial haplogroups in schizophrenia patients compared to their healthy fathers (202 pairs) resulted in an over-representation of the mtDNA lineage cluster, HV, in the patients (p = 0.01), with increased relative risk (odds ratio) of 1.8. Since mitochondrial DNA is small relative to nuclear DNA, a total mitochondrial genome analysis was possible in a hypothesis-free manner. However, mitochondrial DNA haplogroups are highly variable in human population and it will be necessary to replicate our results in other human ethnic groups.