Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

McCauley, Jacob L.; Hahs, Daniel W.; Jiang, Lan; Scott, William K.; Welsh‐Bohmer, Kathleen A.; Jackson, Charles E.; Vance, Jeffery M.; Pericak‐Vance, Margaret A.; Haines, Jonathan L.

doi:10.1186/1471-2350-7-19

Cited by 11 publications

(11 citation statements)

References 65 publications

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“…Data used here were generates as previously described8 and obtained from the ADNI database (www.loni.ucla.edu/ADNI ). The Collaborative Aging and Memory Project (CAMP) subjects are from the Amish communities of central Ohio and northern Indiana9–10. The Columbia University (CU) subjects are a Hispanic cohort described in detail elsewhere11.…”

Section: Methodsmentioning

confidence: 99%

Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes

et al. 2010

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Section: Methodsmentioning

confidence: 99%

Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes

et al. 2010

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“…Additional susceptibility genes and environmental factors are therefore likely to be involved, especially in sporadic AD (SAD) [38,39,41]. In isolated Amish communities, for example, 24 markers have been linked to dementia [33] and several other linkage studies have shown the presence of AD susceptibility genes on chromosomes 9, 10, and 12 [48]. Hence, a small number of AD cases have been linked recently to the chromosome 9 open reading frame 72 (C9ORF72) gene [55].…”

Section: Introductionmentioning

confidence: 99%

Original article Laminar distribution of β-amyloid (Aβ) peptide deposits in the frontal lobe in familial and sporadic Alzheimer’s disease

Armstrong¹

2015

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A b s t r a c t To determine whether genetic factors influence frontal lobe degeneration in Alzheimer's disease (AD), the laminar distributions of diffuse, primitive, and classic β-amyloid (Aβ) peptide deposits were compared in early-onset familial AD (EO-FAD) linked to mutations of the amyloid precursor protein (APP) or presenilin 1 (PSEN1) gene, late-onset familial AD (LO-FAD), and sporadic AD (SAD). The influence of apolipoprotein E (Apo E) genotype on laminar distribution was also studied. In the majority of FAD and SAD cases, maximum density of the diffuse and primitive Aβ deposits occurred in the upper cortical layers, whereas the distribution of the classic Aβ deposits was more variable, either occurring in the lower layers, or a double-peaked (bimodal) distribution was present, density peaks occurring in upper and lower layers. The cortical layer at which maximum density of Aβ deposits occurred and maximum density were similar in EO-FAD, LO-FAD and SAD. In addition, there were no significant differences in distributions in cases expressing

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“…We have used this approach to discover novel susceptibility loci for complex diseases, such as Alzheimer disease and Parkinson’s disease, by studying the Amish communities of Ohio and Indiana [1], [3], [24]–[26]. In a recent genome-wide study using this population [3], 798 successfully genotyped individuals connected into one 13-generation, 4998-member pedigree with consanguineous loops.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, but not surprisingly, significant power is lost when pedigrees are divided. Development of new methods or extensions of current methods to use more pedigree information to perform multipoint linkage analyses or implementation of alternative methods such as identifying identical by descent (IBD) shared segments [26] would greatly improve our ability to query the rich genetic information of founder populations.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Power and Type 1 Error in Large Pedigree Analyses of Binary Traits

et al. 2013

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Studying population isolates with large, complex pedigrees has many advantages for discovering genetic susceptibility loci; however, statistical analyses can be computationally challenging. Allelic association tests need to be corrected for relatedness among study participants, and linkage analyses require subdividing and simplifying the pedigree structures. We have extended GenomeSIMLA to simulate SNP data in complex pedigree structures based on an Amish pedigree to generate the same structure and distribution of sampled individuals. We evaluated type 1 error rates when no disease SNP was simulated and power when disease SNPs with recessive, additive, and dominant modes of inheritance and odds ratios of 1.1, 1.5, 2.0, and 5.0 were simulated. We generated subpedigrees with a maximum bit-size of 24 using PedCut and performed two-point and multipoint linkage using Merlin. We also ran MQLS on the subpedigrees and unified pedigree. We saw no inflation of type 1 error when running MQLS on either the whole pedigrees or the sub-pedigrees, and we saw low type 1 error for two-point and multipoint linkage. Power was reduced when running MQLS on the subpedigrees versus the whole pedigree, and power was low for two-point and multipoint linkage analyses of the subpedigrees. These data suggest that MQLS has appropriate type 1 error rates in our Amish pedigree structure, and while type 1 error does not seem to be affected when dividing the pedigree prior to linkage analysis, power to detect linkage is diminished when the pedigree is divided.

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Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish

Cited by 11 publications

References 65 publications

Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes

Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes

Original article Laminar distribution of β-amyloid (Aβ) peptide deposits in the frontal lobe in familial and sporadic Alzheimer’s disease

Evaluating Power and Type 1 Error in Large Pedigree Analyses of Binary Traits

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