title: GWAS-Linked Loci and Neuroimaging Measures in Alzheimer's Disease.
abstract: Recently, 19 susceptibility loci for Alzheimer's disease (AD) had been identified through AD genome-wide association studies (GWAS) meta-analysis. However, how they influence the pathogenesis of AD still remains largely unknown. We studied those loci with six MRI measures, abnormal glucose metabolism, and β-amyloid (Aβ) deposition on neuroimaging in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database in order to provide clues of the mechanisms through which these genetic variants might be acting. As a result, single nucleotide polymorphisms (SNPs) at rs983392 within MS4A6A and rs11218343 within SOLR1 were both associated with the percentage of increase in the volume of left inferior temporal regions in the follow-up study. Meanwhile, rs11218343 at SORL1 and rs6733839 at BIN1 was associated with rate of volume change of left parahippocampal and right inferior parietal, respectively. Moreover, rs6656401 at CR1 and rs983392 at MS4A6A were both associated with smaller volume of right middle temporal at baseline. However, in addition to the APOE locus, we did not detect any influence on glucose metabolism and Aβ deposition. APOE ε4 allele was associated with almost all measures. Altogether, five loci (rs6656401 at CR1, rs983392within MS4A6A, rs11218343 at SORL1, rs6733839 at BIN1, and APOE ε4) have been detected to be associated with one or a few established AD-related neuroimaging measures.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Tan
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. yu-jintai@163.com.|Memory and Aging Center, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA. yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D059906:Neuroimaging / Q000379:methods*
keywords: Alzheimer’s disease; Aβ deposition; Brain structure; Genome-wide association studies; Glucose metabolism