title: Maternal lineages and Alzheimer disease risk in the Old Order Amish.
abstract: Old Order Amish, founded by a small number of Swiss immigrants, exist in culturally isolated communities across rural North America. The consequences of genetic isolation and inbreeding within this group are evident by increased frequencies of many monogenic diseases and several complex disorders. Conversely, the prevalence of Alzheimer disease (AD), the most common form of dementia, is lower in the Amish than in the general American population. Since mitochondrial dysfunction has been proposed as an underlying cause of AD and a specific haplogroup was found to affect AD susceptibility in Caucasians, we investigated whether inherited mitochondrial haplogroups affect risk of developing AD dementia in Ohio and Indiana Amish communities. Ninety-five independent matrilines were observed across six large pedigrees and three small pedigrees then classified into seven major European haplogroups. Haplogroup T is the most frequent haplogroup represented overall in these maternal lines (35.4%) while observed in only 10.6% in outbred American and European populations. Furthermore, haplogroups J and K are less frequent (1.0%) than in the outbred data set (9.4-11.2%). Affected case matrilines and unaffected control lines were chosen from pedigrees to test whether specific haplogroups and their defining SNPs confer risk of AD. We did not observe frequency differences between AD cases compared to controls overall or when stratified by sex. Therefore, we suggest that the genetic effect responsible for AD dementia in the affected Amish pedigrees is unlikely to be of mitochondrial origin and may be caused by nuclear genetic factors.
authors.affiliation: Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Joelle M
authors.initials: JM
authors.lastname: van der Walt
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Susan
authors.initials: S
authors.lastname: Slifer
authors.forename: P C
authors.initials: PC
authors.lastname: Gaskell
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Welsh-Bohmer
authors.forename: Marilyn
authors.initials: M
authors.lastname: Creason
authors.forename: Amy
authors.initials: A
authors.lastname: Crunk
authors.forename: Denise
authors.initials: D
authors.lastname: Fuzzell
authors.forename: Lynne
authors.initials: L
authors.lastname: McFarland
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kroner
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D002835:Christianity; D004272:DNA, Mitochondrial / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D004272:DNA, Mitochondrial