SIPA1L2 as a risk factor implicated in Alzheimer's disease

Alzheimer's disease(AD) is a common neurodegenerative disorder with high heritability. An increasing number of common variants have been found to be associated with AD, but these common variants can only explain a small proportion of the heritability. Theory and practice have shown that rare variants can explain the remaining heritability. We explored rare functional variants that altering susceptibility to AD among 600470 variants in 389 individuals (175 with AD and 214 with cognitively normal). Firstly, after imputing the missing genotypes on the Michigan imputation server, quality control and gene-based annotation were carried out. Secondly, the efficient resampling sequence kernel association test was performed on 311 annotated exonic variants. Finally, the underlying biological interpretations of the identified risk gene were predicted through several bioinformatics tools. The results showed that under the Bonferroni correction, the rare missense variant rs2275303 in SIPA1L2 gene was significantly associated with AD (P=6.00E-04), and its pathogenicity was verified by bioinformatics analysis. SIPA1L2 gene is expected to play an important role in the prevention, diagnosis, prognosis and treatment of AD.