title: No evidence of association between common European mitochondrial DNA variants in Alzheimer, Parkinson, and migraine in the Spanish population.
abstract: Certain mitochondrial DNA (mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases.
authors.affiliation: Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fachal
authors.forename: Ana
authors.initials: A
authors.lastname: Mosquera-Miguel
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Cubero
authors.forename: Elena
authors.initials: E
authors.lastname: Lorenzo
authors.forename: Agustín
authors.initials: A
authors.lastname: Oterino-Durán
authors.forename: María
authors.initials: M
authors.lastname: Toriello
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quintáns
authors.forename: Montse
authors.initials: M
authors.lastname: Camiña-Tato
authors.forename: Angel
authors.initials: A
authors.lastname: Sesar
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sobrido
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013030:Spain
chemical_list: D004272:DNA, Mitochondrial
keywords: Alzheimer disease; Parkinson disease; SNPs; association studies; false positive; migraine; mitochondrial DNA; population stratification