title: No evidence that major mtDNA European haplogroups confer risk to schizophrenia.
abstract: Previous studies suggest that genetic factors could be involved in mitochondrial dysfunction observed in schizophrenia (SZ), some of them claiming a role of mtDNA common variants (mtSNPs) and/or haplogroups (hgs) in developing this disorder. These studies, however, have mainly been undertaken on relatively small cohorts of patients and control individuals and most have not yet been replicated. To further analyze the role of mtSNPs in SZ risk, we have carried out the largest genotyping effort to date using two Spanish case-control samples comprising a total of 942 schizophrenic patients and 1,231 unrelated controls: 454 patients and 616 controls from Santiago de Compostela (Galicia) and 488 patients and 615 controls from Reus (Catalonia). A set of 25 mtSNPs representing main branches of the European mtDNA phylogeny were genotyped in the Galician cohort and a subset of 16 out of these 25 mtSNPs was genotyped in the Catalan cohort. These 16 common variants characterize the most common European branches of the mtDNA phylogeny. We did not observe any positive association of mtSNPs and hgs with SZ. We discuss several deficiencies of previous studies that might explain the false positive nature of previous findings, including the confounding effect of population sub-structure and deficient statistical methodologies. It is unlikely that mtSNPs defining the most common European mtDNA haplogroups are related to SZ.
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses and Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Mosquera-Miguel
authors.forename: Helena
authors.initials: H
authors.lastname: Torrell
authors.forename: Nerea
authors.initials: N
authors.lastname: Abasolo
authors.forename: Manuel
authors.initials: M
authors.lastname: Arrojo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Paz
authors.forename: Ramón
authors.initials: R
authors.lastname: Ramos-Ríos
authors.forename: Santiago
authors.initials: S
authors.lastname: Agra
authors.forename: Mario
authors.initials: M
authors.lastname: Páramo
authors.forename: Julio
authors.initials: J
authors.lastname: Brenlla
authors.forename: Silvia
authors.initials: S
authors.lastname: Martínez
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
authors.forename: Joaquín
authors.initials: J
authors.lastname: Valero
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutiérrez-Zotes
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martorell
authors.forename: Javier
authors.initials: J
authors.lastname: Costas
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial