Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease

• Published in: Journal of neuroimmunology 2017-09, Vol.310, p.60-65
• Main Authors: Wang, Ke-Sheng, Liu, Ying, Xu, Chun, Liu, Xuefeng, Luo, Xingguang
• Format: Article
• Language: English
• Subjects: Age at onset; Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Apolipoproteins E - genetics; Brain - metabolism; Family Health; Family-based design; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Humans; Male; Middle Aged; mRNA; NAV2; Nerve Tissue Proteins - genetics; Polymorphism, Single Nucleotide - genetics; Polymorphisms; RNA, Messenger - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2017.06.010

The neuron navigator 2 (NAV2) gene is highly expressed in brain and involved in the nervous system development and may play a role in Alzheimer's disease (AD). We aimed to investigate the associations of 317 single-nucleotide polymorphisms (SNPs) in the NAV2 gene with the risk and age at onset (AAO) of AD using a family-based sample (1266 AD cases and 1279 healthy relatives). Association with the risk of AD was assessed using family-based association test -generalized estimating equations (FBAT- GEE) statistics while the association with AAO as a quantitative trait was evaluated using the FBAT-Wilcoxon statistic. Single marker analysis showed that 20 SNPs were significantly associated with the risk of AD (top SNP rs7112354 with p=8.46×10−4) and 11 SNPs were associated with AAO (top SNP rs1354269 with p=2.87×10−3). Interestingly, two SNPs rs17614100 and rs12364788 were associated with both the risk (p=1.7×10−2 and 2.71×10−2; respectively) and AAO (p=1.85×10−3 and 6.06×10−3; respectively). Haplotype analyses further supported the results of single marker analyses. In addition, functional analysis showed that NAV2 mRNA had significant expression across ten human brain regions examined and significantly correlated with APOE expression in four of ten regions. The present study is the first study providing evidence of several genetic variants within the NAV2 gene influencing the risk and AAO of AD. The results of −log(p) values for a single SNP analysis. [Display omitted] •First study of NAV2 gene with age at onset (AAO) of Alzheimer's disease (AD)•Family-based study identified 20 and 11 SNPs with the risk and AAO, respectively.•The top SNP associated with the risk of AD was SNP rs7112354 with p=8.46×10−4.•The most significant SNP associated with the AAO was rs1354269 with p=2.87×10−3.•Two SNPs rs17614100 and rs12364788 were associated with both the risk and AAO.