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P3‐213: Genetic screening in a large cohort of early‐onset Alzheimer's disease patients from Spain: Novel mutations in the amyloid precursor protein and presenilines
Author(s) -
Clarimón Jordi,
Guerreiro Rita,
Lleó Alberto,
Guardia Cristina,
Blesa Rafael,
Gómez-Isla Teresa,
Boada Merce,
Bullido Ma Jesus,
Ferrer Isidre,
Martínez-Lage Pablo,
Masdeu Jose,
Molina Laura,
Molinuevo José Luís,
Pastor Pau,
Pérez-Tur Jordi,
Rey Ma Jesus,
Sánchez-Valle Raquel,
Tàrraga Lluís,
Valdivieso Fernando,
Singleton Andrew,
Hardy John
Publication year - 2008
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.2008.05.1780
Subject(s) - psen1 , early onset alzheimer's disease , genetics , amyloid precursor protein , family history , exon , mutation , age of onset , dementia , mendelian inheritance , medicine , gene , biology , disease , alzheimer's disease
data from the 312k Affymetrix based SNPs for 861 AD cases and 550 controls of Caucasians obtained from the Translational Genomics Research Institute (TGEN). We then compared the linkage and association results from the 2 datasets. Haploview v-4.0, Plink v-1.01, Fbat v-2.0.2c and Merlin v-1.0 were used for our linkage and association analyses. First, we compared the apolipoprotein E (APOE) as a proof of principle, and then we compared the 11 promising candidate regions. Results: In the NIA-LOAD, we were able to detect linkage at 19q13.32, encompassing APOE. Two APOE-locus flanking SNPs (rs11671074 and rs1603) had LODs of 3.1 (p 0.00008) and 3.2 (p 0.00006) respectively. Those SNPs were 608kb and 569kb away from the APOE functional SNPs, respectively. However, the family based and casecontrol based association analyses were not able to detect the signal. When the functional SNPs were used, the 2 SNPs were 5x10-37 and 0.3, respectively. On the other hand, TGEN case-control data showed very strong association with SNP rs4420638, located 11kb away from the APOE functional SNPs (p 1.17x10-35). Conclusions: With a smaller set of SNPs, it is possible to detect the signals either using linkage or association in family based studies; however, with association method, SNPs have to be tightly located and have to be in high linkage disequilibrium (LD) blocks with disease loci.