Author:
Main Leighanne R,Song Yeunjoo E,Lynn Audrey,Laux Renee A,Miskimen Kristy L,Osterman Michael D,Cuccaro Michael L,Ogrocki Paula K,Lerner Alan J,Vance Jeffery M,Fuzzell M Denise,Fuzzell Sarada L,Hochstetler Sherri D,Dorfsman Daniel A,Caywood Laura J,Prough Michael B,Adams Larry D,Clouse Jason E,Herington Sharlene D,Scott William K,Pericak-Vance Margaret A,Haines Jonathan L
Abstract
ABSTRACTINTRODUCTIONAlzheimer disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age.METHODSGenome-wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76-95, who were either cognitively unimpaired (CU) or impaired (CI).RESULTS12 SNPs demonstrated suggestive association (P≤5x10-4) with cognitive preservation. Genetic linkage analyses identified >100 significant (LOD≥3.3) SNPs, some which overlapped with the association results. Only one locus on chromosome 2 retained significance across multiple analyses.DISCUSSIONA novel significant result for cognitive preservation on chromosome 2 includes the genesLRRTM4andCTNNA2. Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulatesLRRTM4andCTNNA2.
Publisher
Cold Spring Harbor Laboratory