%0 Journal Article
%T Genetic Variants in the SORL1 Gene Are Associated with Age at Onset of Alzheimer Disease: A Survival Analysis
%A Ke-Sheng Wang
%A Xuefeng Liu
%A Liang Wang
%A David Briones
%A Chun Xu
%J International Journal of Medical Genetics
%D 2014
%R 10.1155/2014/689832
%X 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 ( ). SNP rs560573, previously associated with the risk of late-onset AD, showed the most association with the AAO in the male sample ( for logrank test and 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 ( and 0.0367, resp.). These findings provide evidence of several genetic variants in SORL1 influencing the AAO of AD. 1. Introduction Alzheimer disease (AD) is the most common form of dementia. Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer¡¯s can occur much earlier [1]. In the United States, the prevalence of AD in 2000 was estimated to be about 1.6% in the 65¨C74 age group, with the rate increasing to 19% in the 75¨C84 age group and to 42% in the greater than 84 age group [2]. The World Health Organization estimated that, in 2005, 0.379% of people worldwide had dementia, and the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030 [3]. Another study estimated that, in 2006, 0.40% of the world population (about 26.6 million) was afflicted by AD, which is predicted to affect 1 in 85 people globally by 2050 [4]. In addition to the disease risk, age at onset (AAO) of AD is also genetically influenced with an estimated heritability of about 42% [5, 6]. Genetic effects account for 57%¨C78% of the variance of AAO [7], while twin studies suggest that the heritability of AD exceeds 60% [8]. AD has a strong genetic predisposition (60¨C80% of the attributable risk) [9]. The sortilin-related receptor (SORL1) gene is located at 11q23.2-q24.2 and is expressed as a 10.5£¿kb transcript in brain, spinal cord, and testis [10]. Rogaeva et al. [11] reported that inherited variants of the SORL1 neuronal sortilin-related receptor were associated with
%U http://www.hindawi.com/journals/ijmg/2014/689832/