Genetic Variants in the SORL1 Gene Are Associated with Age at Onset of Alzheimer Disease: A Survival Analysis

Few studies focused on the association of SORL1 with the age at onset (AAO) of Alzheimer disease (AD). This study investigated the association of 43 SNPs in SORL1 with the AAO of AD by using the Kaplan-Meier survival analysis and the Cox proportional hazards model in SAS version 9.2 and linear regression model in PLINK software (791 AD patients and 782 controls). Both logrank test and Cox regression model showed that five SNPs (rs1784934, rs676759, rs560573, rs593769, and rs11218313) were associated with the AAO of AD in the male sample, while one SNP (rs17125558) was associated with the AAO of AD in the female sample ( P < 0.05 ). SNP rs560573, previously associated with the risk of late-onset AD, showed the most association with the AAO in the male sample ( P = 0.0077 for logrank test and P = 0.0117 in the Cox model). The mean AAO was approximately 2.5 years earlier in individuals who were homozygous for the minor allele compared with those who had at least one major allele. Linear regression model showed that rs2282649 and rs726601 were associated with AAO in the whole sample ( P = 0.0374 and 0.0367, resp.). These findings provide evidence of several genetic variants in SORL1 influencing the AAO of AD.