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.
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This post is Copyright: 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 | July 18, 2024