Rare Coding Variants in PLCG2, ABI3, and TREM2 Are Associated with Alzheimer Disease in the Argentinian Population

DALMASSO MC; BRUSCO, LI; OLIVAR N; MORELLI L

Congreso; AAIC 2018 Chicago-USA; 2018

Alzheimer`s Association

Background: Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer?s disease (AD) in Caucasians. Importantly, it was shown that frequencies and effects of some genetic variants associated with AD vary across ethnicities. Latin American populations are admixture of Native, European, and African ancestors, which present a huge gap in AD genetics studies. Consequently, we explored the effect of these rare coding variants on AD susceptibility in the Southern Cone of South America. Methods: Four rare coding variants, in TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) genes, were genotyped in 419 AD cases and 488 healthy controls from Argentina. Statistical power was increased by including in the analysis 266 Chilean controls. Results: TREM2 rs75932628 and ABI3 rs616338 were validated as risk factors for AD (OR=7.17 [p=0.04] and OR=2.77 [p=0.04], respectively) in this Latin American sample. The PLCG2 rs72824905 showed a suggestive protective effect(OR=0.61 [p=0.39]). Conclusions: Rare coding variants in TREM2, PLCG2, and ABI3also modulate susceptibility to AD in populations from South America, and they mightoriginate from Europe.