Genetic variation in BIN1 gene and Alzheimer's disease risk in Han Chinese individuals

Genome-wide association studies have identified the bridging integrator 1 (BIN1) gene as the most important genetic susceptibility locus in late-onset Alzheimer's disease (LOAD) after apolipoprotein E for individuals of European ancestry. To further characterize this association and to isolate the variants within BIN1 contributing to LOAD in Han Chinese individuals, we conducted a 2-step design study in our cohort of 1133 LOAD patients and 1159 control subjects. Sequencing analysis identified 44 variants within BIN1. Follow-up genotyping analysis revealed that a novel missense mutation P318L appeared to exert risk effect for development of LOAD; and rs67327804 was also significantly associated with LOAD risk even after adjusting for age, gender, and apolipoprotein E epsilon 4 status. Haplotype analysis confirmed that the "GA" haplotype derived from single-nucleotide polymorphisms in rs67327804 and rs1060743 showed a 1.4-fold increased risk of LOAD. Our findings provided the first independent evidence that variants in BIN1 were significantly associated with LOAD in Han Chinese individuals. (C) 2014 Elsevier Inc. All rights reserved.