@article{c8919ee5281246c0a96b9baf391069e4,
title = "Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium",
abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.",
keywords = "Aged, Aged, 80 and over, Aging/genetics, Apolipoproteins E/genetics, Claudin-5/genetics, Cohort Studies, Female, Genome-Wide Association Study, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Memory Disorders/genetics, Middle Aged, Polymorphism, Single Nucleotide/genetics, Proteins/genetics, Proteoglycans/genetics, Regression Analysis, Sulfotransferases/genetics, Verbal Learning/physiology",
author = "St{\'e}phanie Debette and {Ibrahim Verbaas}, {Carla A} and Jan Bressler and Maaike Schuur and Albert Smith and Bis, {Joshua C} and Gail Davies and Christiane Wolf and Vilmundur Gudnason and Chibnik, {Lori B} and Qiong Yang and deStefano, {Anita L} and {de Quervain}, {Dominique J F} and Velandai Srikanth and Jari Lahti and Grabe, {Hans J} and Smith, {Jennifer A} and Lutz Priebe and Lei Yu and Nazanin Karbalai and Caroline Hayward and Wilson, {James F} and Harry Campbell and Katja Petrovic and Myriam Fornage and Ganesh Chauhan and Robin Yeo and Ruth Boxall and James Becker and Oliver Stegle and Mather, {Karen A} and Vincent Chouraki and Qi Sun and Rose, {Lynda M} and Susan Resnick and Christopher Oldmeadow and Mirna Kirin and Wright, {Alan F} and Jonsdottir, {Maria K} and Rhoda Au and Albert Becker and Najaf Amin and Nalls, {Mike A} and Turner, {Stephen T} and Kardia, {Sharon L R} and Ben Oostra and Gwen Windham and Coker, {Laura H} and Wei Zhao and Knopman, {David S} and Gerardo Heiss and Griswold, {Michael E} and Gottesman, {Rebecca F} and Veronique Vitart and Hastie, {Nicholas D} and Lina Zgaga and Igor Rudan and Ozren Polasek and Holliday, {Elizabeth G} and Peter Schofield and Choi, {Seung Hoan} and Toshiko Tanaka and Yang An and Perry, {Rodney T} and Kennedy, {Richard E} and Sale, {Mich{\`e}le M} and Jing Wang and Wadley, {Virginia G} and Liewald, {David C} and Ridker, {Paul M} and Gow, {Alan J} and Alison Pattie and Starr, {John M} and David Porteous and Xuan Liu and Russell Thomson and Armstrong, {Nicola J} and Gudny Eiriksdottir and Assareh, {Arezoo A} and Kochan, {Nicole A} and Elisabeth Widen and Aarno Palotie and Yi-Chen Hsieh and Eriksson, {Johan G} and Christian Vogler and {van Swieten}, {John C} and Shulman, {Joshua M} and Alexa Beiser and Jerome Rotter and Schmidt, {Carsten O} and Wolfgang Hoffmann and N{\"o}then, {Markus M} and Luigi Ferrucci and John Attia and Uitterlinden, {Andre G} and Philippe Amouyel and Jean-Fran{\c c}ois Dartigues and H{\'e}l{\`e}ne Amieva and Katri R{\"a}ikk{\"o}nen and Melissa Garcia and Wolf, {Philip A} and Albert Hofman and Longstreth, {W T} and Psaty, {Bruce M} and Eric Boerwinkle and DeJager, {Philip L} and Sachdev, {Perminder S} and Reinhold Schmidt and Breteler, {Monique M B} and Alexander Teumer and Lopez, {Oscar L} and Sven Cichon and Chasman, {Daniel I} and Francine Grodstein and Bertram M{\"u}ller-Myhsok and Christophe Tzourio and Andreas Papassotiropoulos and Bennett, {David A} and Ikram, {M Arfan} and Deary, {Ian J} and {van Duijn}, {Cornelia M} and Lenore Launer and Fitzpatrick, {Annette L} and Sudha Seshadri and Mosley, {Thomas H} and {Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium}",
note = "Copyright {\textcopyright} 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = apr,
day = "15",
doi = "10.1016/j.biopsych.2014.08.027",
language = "English",
volume = "77",
pages = "749--63",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "8",
}