Affiliations: [a] Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| [b] Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China
| [c] Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China
| [d] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China.
Correspondence:
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Correspondence to: Jianping Jia, MD, PhD, Professor and Director, Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, China. Tel.: +86 10 83199449; Fax: +86 10 83128678; E-mail: jjp@ccmu.edu.cn.
Note: [1] These authors contributed equally to this work.
Abstract: Background:The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective:This study aims to determine how race and APOE genotype affect the risks for AD. Methods:We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results:The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion:Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.
