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.
| Original language | English |
|---|---|
| Pages (from-to) | 115-122 |
| Number of pages | 8 |
| Journal | Human genetics. |
| Volume | 118 |
| Issue number | 1 |
| State | Published - Oct 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Maternal lineages and Alzheimer disease risk in the Old Order Amish. / van der Walt, Joelle M.; Scott, William K; Slifer, Susan; Gaskell, P. C.; Martin, Eden R; Welsh-Bohmer, Kathleen; Creason, Marilyn; Crunk, Amy; Fuzzell, Denise; McFarland, Lynne; Kroner, Charles C.; Jackson, C. E.; Haines, Jonathan L.; Pericak-Vance, Margaret A.
In: Human genetics., Vol. 118, No. 1, 01.10.2005, p. 115-122.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Maternal lineages and Alzheimer disease risk in the Old Order Amish.
AU - van der Walt, Joelle M.
AU - Scott, William K
AU - Slifer, Susan
AU - Gaskell, P. C.
AU - Martin, Eden R
AU - Welsh-Bohmer, Kathleen
AU - Creason, Marilyn
AU - Crunk, Amy
AU - Fuzzell, Denise
AU - McFarland, Lynne
AU - Kroner, Charles C.
AU - Jackson, C. E.
AU - Haines, Jonathan L.
AU - Pericak-Vance, Margaret A
PY - 2005/10/1
Y1 - 2005/10/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33646156243&partnerID=8YFLogxK
M3 - Article
C2 - 16078048
AN - SCOPUS:33646156243
VL - 118
SP - 115
EP - 122
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 1
ER -