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[P3–100]: ALZHEIMER's DISEASE, PARKINSON's DISEASE AND FRONTOTEMPORAL DEMENTIA: POLYGENICITY AND PLEIOTROPY
Author(s) -
Ferrari Raffaele,
Wang Yunpeng,
Vandrovcova Jana,
Dale Anders M.,
Andreassen Ole,
Miller Bruce L.,
Hardy John,
Desikan Rahul S.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1310
Subject(s) - pleiotropy , frontotemporal dementia , haplotype , single nucleotide polymorphism , neurodegeneration , disease , genetics , genetic association , biology , genome wide association study , odds ratio , dementia , allele , medicine , genotype , gene , phenotype
discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions, and compared the two sets of criteria. Methods:We used data from the Adult Changes in Thought (ACT) study including DSM-IV criteria for dementia status, McKhann et al. criteria for clinical Alzheimer’s Disease, and Braak and CERAD findings on neurofibrillary tangles and neuritic plaques to categorize the 621 ACT participants of European ancestry who died and came to autopsy. We applied ADSP discovery and replication definitions to identify controls, cases, and people who were neither controls nor cases. Results: There was some agreement between the discovery and replication definitions (see Table). Major areas of discrepancy included the finding that only 40% of the discovery sample controls had sufficiently low levels of neurofibrillary tangles and neuritic plaques to be considered controls by the replication criteria, and the finding that 16% of the replication phase cases were diagnosed with non-AD dementia during life and thus were excluded as cases for the discovery phase. Conclusions:These findings should inform interpretation of genetic association findings from the ADSP. Differences in genetic association findings between the two phases of the study may reflect these different phenotype definitions from the discovery and replication phase of the ADSP.