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[O2–08–06]: CONTRIBUTION OF RARE DELETERIOUS ABCA7 MUTATIONS TO A BELGIAN EARLY‐ONSET ALZHEIMER's DISEASE COHORT
Author(s) -
Van den Bossche Tobi,
De Roeck Arne,
Sieben Anne,
Martin JeanJacques,
Vandenberghe Rik,
Engelborghs Sebastiaan,
De Deyn Peter Paul,
Sleegers Kristel,
Cras Patrick,
Van Broeckhoven Christine
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.2017.07.191
Subject(s) - penetrance , cohort , dementia , mutation , medicine , family history , genetics , oncology , biology , disease , gene , phenotype
onset AD cases for the identification of novel variants and genes implicated on AD. Methods:We have performed whole-exome or whole-genome sequencing on 1,077 clinically diagnosed LOAD and 440 non-demented relatives. All samples were recruited by the Knight ADRC or the NIA-LOAD family study group. Variant discovery was performed following GATK’s best practice followed by stringent quality control. We focused our analysis on nonsynonymous variants with a minor allele frequency <1% in the general population (ExAC). We perform genome-wide scans to examine the presence of causative and low frequency coding variants in the most common neurodegenerative diseases, as well as in novel candidate genes. Results:Known pathogenic mutations were found in 4.42% of the families as well as an enrichment of non-synonymous variants in AD and frontotemporal lobular dementia (FTLD) genes. We have detected potential risk variants that present perfect segregation in several families of 7 members in addition to few novel candidate genes with genome-wide significance associated to disease risk. Conclusions:Known pathogenic and low frequency coding variants in AD, FTD and PD genes can be found in clinical AD cases; indicating that more stringent selecting criteria and genetic testing must be performed before incorporating new samples into analysis. We have identified some preliminary candidate variants and genes that would confer risk to AD; network analysis and replication are underway.