Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Abstract Recent genome-wide association studies have identified 5 loci ( BIN1 , CLU , CR1 , EXOC3L2 , and PICALM ) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1 , EXO2CL3 , and PICALM . In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1 ) and rs541458 (for PICALM ) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [CI] [1.15–1.38], p = 2.9 × 10−7 , and OR = 0.80, 95% CI [0.74–0.88], p = 4.6 × 10−7 , respectively). In a meta-analysis, rs597668 ( EXOC3L2 ) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% CI [1.06–1.32], p = 2.0 × 10−3 ). However, this signal did not appear to be independent of APOE . In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation.