title: MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association.
abstract: Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls. Our findings support the association of mtDNA haplogroups and recurrent variants with specific phenotypes such as Parkinson's disease, type 2 diabetes, longevity, and breast cancer. Strikingly, our assessment of mtDNA variants' involvement with multiple phenotypes revealed significant impact for Caucasian haplogroups H, J, and K. Therefore, ancient mtDNA variants could be divided into those that affect specific phenotypes, versus others with a general impact on phenotype combinations. We suggest that the mtDNA could serve as a model for phenotype specificity versus allele heterogeneity.
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Marom
authors.affiliation: Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Friger
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D044465:White People
chemical_list: D004272:DNA, Mitochondrial