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Genome‐wide association study of Alzheimer's disease endophenotypes at prediagnosis stages
Author(s) -
Chung Jaeyoon,
Wang Xulong,
Maruyama Toru,
Ma Yiyi,
Zhang Xiaoling,
Mez Jesse,
Sherva Richard,
Takeyama Haruko,
Lunetta Kathryn L.,
Farrer Lindsay A.,
Jun Gyungah R.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.11.006
Subject(s) - endophenotype , dementia , single nucleotide polymorphism , alzheimer's disease , genome wide association study , genetic association , disease , neuroimaging , alzheimer's disease neuroimaging initiative , episodic memory , cognition , cognitive impairment , allele , medicine , psychology , oncology , neuroscience , genetics , genotype , biology , gene
Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated. Methods We conducted genome‐wide association studies for AD‐related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aβ 42 and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study. Results In CN subjects, study‐wide significant ( P < 8.3 × 10 −9 ) loci were identified for total tau near SRRM4 and C14orf79 and for hippocampal volume near MTUS1 . In mild cognitive impairment subjects, study‐wide significant association was found with single nucleotide polymorphisms (SNPs) near ZNF804B for logical memory test of delayed recall scores. We found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls. Discussion Our findings for AD‐related brain changes before AD provide insight about early AD‐related biological processes.