Genome-Wide Association Study Identifies SLAMF1 Affecting the Rate of Memory Decline

Article type: Research Article

Authors: Chen, Shi-Dong^a | Li, Hong-Qi^a | Shen, Xue-Ning^a | Li, Jie-Qiong^b | Xu, Wei^c | Huang, Yu-Yuan^a | Tan, Lan^c | Dong, Qiang^{a; *} | Yu, Jin-Tai^{a; *} | on behalf of Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [b] Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China | [c] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

Correspondence: [] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, or Prof. Qiang Dong, MD, PhD Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn (J.T. Yu); E-mail: dong_qiang@fudan.edu.cn (Q. Dong).

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:As cognitive function declines with age, identifying factors affecting the trajectory of cognitive decline is an indispensable step toward developing intervention strategies to improve the quality of the elderly life. Objective:We performed a genome-wide association study (GWAS) focusing on memory function to explore single nucleotide polymorphisms (SNPs) associated with the rate of memory decline. Methods:Seven hundred and nine eligible non-Hispanic Caucasians from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included for analysis after quality control. GWAS was performed with linear regression. We subsequently tested whether the associations remained significant in subgroup analysis and also examined the impact of SNPs on the longitudinal changes in other neuropsychological measures and amyloid pathology. Results:We identified rs13374761-A in SLAMF1 gene associated with less memory decline (MAF = 0.071, β= 0.0103, p = 4.14×10–8). Subgroup analysis showed stability of results across groups with different diagnosis at baseline. Rs13374761-A also had protective effects on global cognition (p = 0.024), episodic memory (p = 0.024), and semantic memory (p = 0.042), and exerts protection against a decrease in CSF Aβ42 concentration (p = 0.0463) and an increase in Aβ loading in cerebral cortex (p = 0.00666) among minor allele carriers. Conclusion:A novel variant in gene SLAMF1 affects the rate of memory decline in the aged population. Given the protective effect of this variant, SLAMF1 should be further investigated as a potential preventive and therapeutic target for monitoring cognition trajectories.

Keywords: Alzheimer’s disease, amyloid, cognitive decline, genome-wide association study, memory, SLAMF1, SNP

DOI: 10.3233/JAD-191214

Journal: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 139-149, 2020