title: Mitochondrial haplotypes associated with biomarkers for Alzheimer's disease.
abstract: Various studies have suggested that the mitochondrial genome plays a role in late-onset Alzheimer's disease, although results are mixed. We used an endophenotype-based approach to further characterize mitochondrial genetic variation and its relationship to risk markers for Alzheimer's disease. We analyzed longitudinal data from non-demented, mild cognitive impairment, and late-onset Alzheimer's disease participants in the Alzheimer's Disease Neuroimaging Initiative with genetic, brain imaging, and behavioral data. We assessed the relationship of structural MRI and cognitive biomarkers with mitochondrial genome variation using TreeScanning, a haplotype-based approach that concentrates statistical power by analyzing evolutionarily meaningful groups (or clades) of haplotypes together for association with a phenotype. Four clades were associated with three different endophenotypes: whole brain volume, percent change in temporal pole thickness, and left hippocampal atrophy over two years. This is the first study of its kind to identify mitochondrial variation associated with brain imaging endophenotypes of Alzheimer's disease. Our results provide additional evidence that the mitochondrial genome plays a role in risk for Alzheimer's disease.
authors.affiliation: Department of Biology, Brigham Young University, Provo, Utah, United States of America ; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, United States of America.
authors.forename: Perry G
authors.initials: PG
authors.lastname: Ridge
authors.forename: Andre
authors.initials: A
authors.lastname: Koop
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Maxwell
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Bailey
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: John S K
authors.initials: JS
authors.lastname: Kauwe
authors.forename: Robyn A
authors.initials: RA
authors.lastname: Honea
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D015233:Models, Statistical; D012307:Risk Factors; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers
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