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Maternal lineages and Alzheimer disease risk in the Old Order Amish

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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.

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Acknowledgements

We are grateful to all participants of this study. We also thank the personnel at the Center for Human Genetics at Duke University Medical Center. This research was supported by a grant from the McKnight Endowment Fund for Neuroscience and a Zenith award from the Alzheimer’s Association. Additional support was provided from the National Institutes of Health (AG19085, AG05128, AG11268, AG19726) and the Alzheimer’s Disease Research Center (II-RG94101, RG2-96044, II-RG00-05, TLL-97-012). Some of this work was supported by a GCRC grant award (RR00095) to Vanderbilt University.

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Authors and Affiliations

  1. Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC, 27710, USA

    Joelle M. van der Walt, William K. Scott, Susan Slifer, P. C. Gaskell, Eden R. Martin, Kathleen Welsh-Bohmer, Charles C. Kroner & Margaret A. Pericak-Vance

  2. Program in Human Genetics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Marilyn Creason, Amy Crunk, Denise Fuzzell, Lynne McFarland & Jonathan L. Haines

  3. Department of Medicine Scott & White Memorial Hospital, Temple, TX, USA

    C. E. Jackson

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  1. Joelle M. van der Walt
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  2. William K. Scott
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  4. P. C. Gaskell
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  5. Eden R. Martin
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  6. Kathleen Welsh-Bohmer
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  7. Marilyn Creason
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  8. Amy Crunk
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  9. Denise Fuzzell
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  10. Lynne McFarland
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  11. Charles C. Kroner
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  12. C. E. Jackson
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  13. Jonathan L. Haines
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  14. Margaret A. Pericak-Vance
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Correspondence to Margaret A. Pericak-Vance.

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van der Walt, J.M., Scott, W.K., Slifer, S. et al. Maternal lineages and Alzheimer disease risk in the Old Order Amish. Hum Genet 118, 115–122 (2005). https://doi.org/10.1007/s00439-005-0032-x

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