Affiliations: [a] Department of Neurology, Affiliated Hospital of Taishan Medical College, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taian, Shandong, China
| [b] School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| [c] Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon, Korea
| [d] Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China
Correspondence:
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Correspondence to: Bao-liang Sun and Xiao-yi Yang, Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China; Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong 271000, China. Tel.: +86 538 622 7116; Fax: +86 538 621 0185; E-mails: blsun88@163.com (B.-L. Sun); xyyang@tsmc.edu.cn (X.-Y. Yang).
Abstract: A recent study sequenced the full coding region of SORL1 in 1,255 early-onset Alzheimer’s disease (EOAD) cases and 1,938 control individuals, and investigated the contribution of genetic variability in SORL1 to EOAD risk in a European cohort. This study identified six common variants and five low frequency variants in the SORL1 coding sequence. However, none of these 11 variants was significantly associated with EOAD risk after adjusting for multiple testing. We consider whether these 11 SORL1 variants identified in European EOAD contribute to late-onset Alzheimer’s disease (LOAD) risk in individuals of European ancestry. Here, we investigated these 11 SORL1 variants identified in European EOAD and LOAD risk in individuals of European ancestry using a large-scale LOAD GWAS. Our results indicate that three genetic variants rs2070045, rs2276412, and rs17125548 as well as their tagged genetic variants contribute to LOAD risk in European population. We further investigate whether these variants could affect SORL1 expression using multiple expression quantitative trait loci (eQTLs) datasets. Our findings suggest that three genetic variants rs2070045, rs1699102, and rs3824968 could significantly regulate SORL1 expression in human brain tissues. We believe that our findings further provide important supplementary information about the involvement of the SORL1 variants in LOAD risk.
Keywords: Alzheimer’s disease, genome-wide association studies, SORL1
