@article{cb641434cfd84980b5212d64dcac7d69,
title = "Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages",
abstract = " Introduction: 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.",
keywords = "ADNI, Alzheimer's disease, Biomarker, Cerebrospinal fluid, Coexpression network, Endophenotypes, Genome-wide association, Logical memory, MRI, Tau",
author = "{The Alzheimer's Disease Neuroimaging Initiative} and Jaeyoon Chung and Xulong Wang and Toru Maruyama and Yiyi Ma and Xiaoling Zhang and Jesse Mez and Richard Sherva and Haruko Takeyama and Lunetta, {Kathryn L.} and Farrer, {Lindsay A.} and Jun, {Gyungah R.}",
note = "Funding Information: This study was supported in part by National Institutes of Health (NIH) grants RF1-AG057519, R01-AG048927, U01-AG032984, UF1-AG046198, and P30-AG13846. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; NIH Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. The authors thank Eisai Bio Bank, the University of Miami Brain Endowment Bank, and the Harvard Brain Tissue Resource Center, funded through NIH-NeuroBioBank HHSN-271-2013-00030C the National Institute of Mental Health (NIMH), National Institute of Neurological Diseases and Stroke (NINDS), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and brain donors and their families for the tissue samples used in these studies. Funding Information: This study was supported in part by National Institutes of Health (NIH) grants RF1-AG057519 , R01-AG048927 , U01-AG032984 , UF1-AG046198 , and P30-AG13846 . Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; NIH Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. The authors thank Eisai Bio Bank, the University of Miami Brain Endowment Bank, and the Harvard Brain Tissue Resource Center, funded through NIH-NeuroBioBank HHSN-271-2013-00030C the National Institute of Mental Health (NIMH), National Institute of Neurological Diseases and Stroke (NINDS), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and brain donors and their families for the tissue samples used in these studies. Publisher Copyright: {\textcopyright} 2017 the Alzheimer's Association",
year = "2018",
month = may,
doi = "10.1016/j.jalz.2017.11.006",
language = "English",
volume = "14",
pages = "623--633",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "5",
}
