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Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.

Debette, Stéphanie and Ibrahim Verbaas, Carla A. and Bressler, Jan and Schuur, Maaike and Smith, Albert and Bis, Joshua C. and Davies, Gail and Wolf, Christiane and Gudnason, Vilmundur and Chibnik, Lori B. and Yang, Qiong and deStefano, Anita L. and de Quervain, Dominique J. F. and Srikanth, Velandai and Lahti, Jari and Grabe, Hans J. and Smith, Jennifer A. and Priebe, Lutz and Yu, Lei and Karbalai, Nazanin and Hayward, Caroline and Wilson, James F. and Campbell, Harry and Petrovic, Katja and Fornage, Myriam and Chauhan, Ganesh and Yeo, Robin and Boxall, Ruth and Becker, James and Stegle, Oliver and Mather, Karen A. and Chouraki, Vincent and Sun, Qi and Rose, Lynda M. and Resnick, Susan and Oldmeadow, Christopher and Kirin, Mirna and Wright, Alan F. and Jonsdottir, Maria K. and Au, Rhoda and Becker, Albert and Amin, Najaf and Nalls, Mike A. and Turner, Stephen T. and Kardia, Sharon L. R. and Oostra, Ben and Windham, Gwen and Coker, Laura H. and Zhao, Wei and Knopman, David S. and Heiss, Gerardo and Griswold, Michael E. and Gottesman, Rebecca F. and Vitart, Veronique and Hastie, Nicholas D. and Zgaga, Lina and Rudan, Igor and Polasek, Ozren and Holliday, Elizabeth G. and Schofield, Peter and Choi, Seung Hoan and Tanaka, Toshiko and An, Yang and Perry, Rodney T. and Kennedy, Richard E. and Sale, Michèle M. and Wang, Jing and Wadley, Virginia G. and Liewald, David C. and Ridker, Paul M. and Gow, Alan J. and Pattie, Alison and Starr, John M. and Porteous, David and Liu, Xuan and Thomson, Russell and Armstrong, Nicola J. and Eiriksdottir, Gudny and Assareh, Arezoo A. and Kochan, Nicole A. and Widen, Elisabeth and Palotie, Aarno and Hsieh, Yi-Chen and Eriksson, Johan G. and Vogler, Christian and van Swieten, John C. and Shulman, Joshua M. and Beiser, Alexa and Rotter, Jerome and Schmidt, Carsten O. and Hoffmann, Wolfgang and Nöthen, Markus M. and Ferrucci, Luigi and Attia, John and Uitterlinden, Andre G. and Amouyel, Philippe and Dartigues, Jean-François and Amieva, Hélène and Räikkönen, Katri and Garcia, Melissa and Wolf, Philip A. and Hofman, Albert and Longstreth, W. T. and Psaty, Bruce M. and Boerwinkle, Eric and DeJager, Philip L. and Sachdev, Perminder S. and Schmidt, Reinhold and Breteler, Monique M. B. and Teumer, Alexander and Lopez, Oscar L. and Cichon, Sven and Chasman, Daniel I. and Grodstein, Francine and Müller-Myhsok, Bertram and Tzourio, Christophe and Papassotiropoulos, Andreas and Bennett, David A. and Ikram, M. Arfan and Deary, Ian J. and van Duijn, Cornelia M. and Launer, Lenore and Fitzpatrick, Annette L. and Seshadri, Sudha and Mosley, Thomas H. and Cohorts for Heart, and Aging Research in Genomic Epidemiology Consortium, . (2015) Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Biological psychiatry, 77 (8). pp. 749-763.

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Official URL: http://edoc.unibas.ch/40793/

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Abstract

Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.; We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults.; rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism.; This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:de Quervain, Dominique J.-F. and Papassotiropoulos, Andreas
Item Type:Article, refereed
Publisher:Elsevier
Corporate Creators:Cohorts for Heart, Aging Research in Genomic Epidemiology Consortium
ISSN:1873-2402
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Jun 2016 11:01
Deposited On:02 Feb 2016 13:13

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