Genome-wide Meta-analysis Identifies Ancestry-specific Loci for Alzheimer's Disease

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Jul 18

PMID 39023044

Authors

Yi-Jun Ge

Shi-Dong Chen

Bang-Sheng Wu

Ya-Ru Zhang

Jun Wang

Xiao-Yu He

Wei-Shi Liu

Yi-Lin Chen

Ya-Nan Ou

Xue-Ning Shen

Yu-Yuan Huang

Yi-Han Gan

Liu Yang

Ling-Zhi Ma

Ya-Hui Ma

Ke-Liang Chen

Shu-Fen Chen

Mei Cui

Lan Tan

Qiang Dong

Qian-Hua Zhao

Yan-Jiang Wang

Jian-Ping Jia

Jin-Tai Yu

Affiliations

Soon will be listed here.

Abstract

Introduction: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry.

Methods: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals.

Results: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD.

Discussion: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology.

Highlights: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Citing Articles

Variables associated with cognitive function: an exposome-wide and mendelian randomization analysis.

Zhao Y, Hao Y, Ge Y, Zhang Y, Huang L, Fu Y Alzheimers Res Ther. 2025; 17(1):13.

PMID: 39773296 PMC: 11706180. DOI: 10.1186/s13195-025-01670-5.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

Ge Y, Chen S, Wu B, Zhang Y, Wang J, He X Alzheimers Dement. 2024; 20(9):6243-6256.

PMID: 39023044 PMC: 11497642. DOI: 10.1002/alz.14121.

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