A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals

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.