A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals.
11 affiliations
- 1Center for Clinical Research and Biostatistics, JC School of Public Health and Primary Care (JCSPHPC), The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China. [email protected].
- 2CUHK Shenzhen Research Institute, No. 10 Yuexing 2nd Road, Shenzhen, 518172, China. [email protected].
- 3Beth Bioinformatics Co. Ltd, Hong Kong SAR, China.
- 4School of Medicine, Warshel Institute for Computational Biology, The Chinese University of Hong Kong (CUHK-SZ), 2001 Longxiang Road, Shenzhen, 518172, China.
- 5Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou, 310051, China.
- 6Center for Clinical Research and Biostatistics, JC School of Public Health and Primary Care (JCSPHPC), The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.
- 7CUHK Shenzhen Research Institute, No. 10 Yuexing 2nd Road, Shenzhen, 518172, China.
- 8Department of Anaesthesia and Intensive Care, CUHK, Hong Kong SAR, China.
- 9Li Ka Shing Institute of Health Sciences, CUHK, Hong Kong SAR, China.
- 10State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases and Department of Medicine and Therapeutics, CUHK, Hong Kong SAR, China.
- 11Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou, 310051, China. [email protected].
Abstract
While genetic heritability plays a major role in the development of cognitive impairment, most genetic risk factors are identified from studies of European populations. We conducted a genome-wide association study (GWAS) on cognitive impairment in the Chinese population by sequencing 1,040 matched case-control individuals from a longitudinal cohort of Zhejiang Province, China. We detected 19 SNPs clustered in 15 genomic loci reaching suggestive significance (P < 1 × 10- 5). Eleven of these genomic loci are newly associated with Alzheimer's disease (AD) or cognitive impairment, among which five (GRP39, FAT1, EDIL3, ZNF596, and PDGFD) show nominal evidence of replication in both external GWAS of AD in East-Asian populations and summary statistics of AD in diverse populations. The detected loci are implicated in micronutrient homeostasis including zinc (GPR39), iron (STEAP1), potassium (KCNJ6), and vitamin K (VKORC1L1), cell connections (EVPLL) through cadherin regulations (PCDH18, FAT1), regulating amyloid-beta precursor protein (APP) (EDIL3), formation of amyloid-β (EDEM1) and neurofibrillary tangles (PDGFD, ZNF596), neuronal growth (NEGR1), and phosphatase regulations (SETBP1, TPTE). This study presents a robust GWAS for cognitive impairment in the Chinese population and highlights a promising set of therapeutic targets for neurodegenerative disorder.
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BibTeX
@article{wang2026genomewide,
title = {{A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals.}},
author = {Maggie Haitian Wang and Yexian Zhang and Rui Sun and Fudong Li and Tao Zhang and Xue Gu and Jingzhi Lou and Lirong Cao and Shimin Su and Hong Zheng and Caiqi Liu and Marc Ka Chun Chong and William Ka Kei Wu and Jun Yu and Benny Chung-Ying Zee and Junfen Lin},
journal = {Human genetics},
year = {2026},
month = oct,
doi = {10.1007/s00439-026-02887-6},
url = {https://europepmc.org/article/MED/42888346},
note = {CC BY},
}
RIS
TY - JOUR
TI - A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals.
AU - Maggie Haitian Wang
AU - Yexian Zhang
AU - Rui Sun
AU - Fudong Li
AU - Tao Zhang
AU - Xue Gu
AU - Jingzhi Lou
AU - Lirong Cao
AU - Shimin Su
AU - Hong Zheng
AU - Caiqi Liu
AU - Marc Ka Chun Chong
AU - William Ka Kei Wu
AU - Jun Yu
AU - Benny Chung-Ying Zee
AU - Junfen Lin
PY - 2026
DA - 2026/10/17
JO - Human genetics
DO - 10.1007/s00439-026-02887-6
UR - https://europepmc.org/article/MED/42888346
AB - While genetic heritability plays a major role in the development of cognitive impairment, most genetic risk factors are identified from studies of European populations. We conducted a genome-wide association study (GWAS) on cognitive impairment in the Chinese population by sequencing 1,040 matched case-control individuals from a longitudinal cohort of Zhejiang Province, China. We detected 19 SNPs clustered in 15 genomic loci reaching suggestive significance (P < 1 × 10- 5). Eleven of these genomic loci are newly associated with Alzheimer's disease (AD) or cognitive impairment, among which five (GRP39, FAT1, EDIL3, ZNF596, and PDGFD) show nominal evidence of replication in both external GWAS of AD in East-Asian populations and summary statistics of AD in diverse populations. The detected loci are implicated in micronutrient homeostasis including zinc (GPR39), iron (STEAP1), potassium (KCNJ6), and vitamin K (VKORC1L1), cell connections (EVPLL) through cadherin regulations (PCDH18, FAT1), regulating amyloid-beta precursor protein (APP) (EDIL3), formation of amyloid-β (EDEM1) and neurofibrillary tangles (PDGFD, ZNF596), neuronal growth (NEGR1), and phosphatase regulations (SETBP1, TPTE). This study presents a robust GWAS for cognitive impairment in the Chinese population and highlights a promising set of therapeutic targets for neurodegenerative disorder.
SN - 0340-6717
SN - 1432-1203
ER -