Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

Debette, Stéphanie, Ibrahim Verbaas, Carla A., Bressler, Jan, Schuur, Maaike, Smith, Albert, Bis, Joshua C., Davies, Gail, Wolf, Christiane, Gudnason, Vilmundur, Chibnik, Lori B., Yang, Qiong, deStefano, Anita L., de Quervain, Dominique J.F., Srikanth, Velandai, Lahti, Jari, Grabe, Hans J., Smith, Jennifer A., Priebe, Lutz, Yu, Lei, Karbalai, Nazanin, Hayward, Caroline, Wilson, James F., Campbell, Harry, Petrovic, Katja, Fornage, Myriam, Chauhan, Ganesh, Yeo, Robin, Boxall, Ruth, Becker, James, Stegle, Oliver, Mather, Karen A., Chouraki, Vincent, Sun, Qi, Rose, Lynda M., Resnick, Susan, Oldmeadow, Christopher, Kirin, Mirna, Wright, Alan F., Jonsdottir, Maria K., Au, Rhoda, Becker, Albert, Amin, Najaf, Nalls, Mike A., Turner, Stephen T., Kardia, Sharon L.R., Oostra, Ben, Windham, Gwen, Coker, Laura H., Zhao, Wei, Knopman, David S., Heiss, Gerardo, Griswold, Michael E., Gottesman, Rebecca F., Vitart, Veronique, Hastie, Nicholas D., Zgaga, Lina, Rudan, Igor, Polasek, Ozren, Holliday, Elizabeth G., Schofield, Peter, Choi, Seung Hoan, Tanaka, Toshiko, An, Yang, Perry, Rodney T., Kennedy, Richard E., Sale, Michèle M., Wang, Jing, Wadley, Virginia G., Liewald, David C., Ridker, Paul M., Gow, Alan J., Pattie, Alison, Starr, John M., Porteous, David, Liu, Xuan, Thomson, Russell, Armstrong, Nicola J., Eiriksdottir, Gudny, Assareh, Arezoo A., Kochan, Nicole A., Widen, Elisabeth, Palotie, Aarno, Hsieh, Yi-Chen, Eriksson, Johan G., Vogler, Christian, van Swieten, John C., Shulman, Joshua M., Ferrucci, Luigi, Attia, John, Uitterlinden, Andre G., Amouyel, Philippe, Dartigues, Jean-François, Amieva, Hélène, Räikkönen, Katri, Garcia, Melissa, Wolf, Philip A., Hofman, Albert, Longstreth Jr, W.T., Psaty, Bruce M., Boerwinkle, Eric, DeJager, Philip L., Sachdev, Perminder S., Schmidt, Reinhold, Breteler, Monique M.B., Teumer, Alexander, Lopez, Oscar L., Cichon, Sven, Papassotiropoulos, Andreas, Bennett, David A., Ikram, M. Arfan, Deary, Ian J., van Duijn, Cornelia M., Launer, Lenore, Fitzpatrick, Annette L., Seshadri, Sudha, Mosley Jr, Thomas H., for the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and Brown, Matthew A. (2014) 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: 749-763. doi:10.1016/j.biopsych.2014.08.027

Author Debette, Stéphanie
Ibrahim Verbaas, Carla A.
Bressler, Jan
Schuur, Maaike
Smith, Albert
Bis, Joshua C.
Davies, Gail
Wolf, Christiane
Gudnason, Vilmundur
Chibnik, Lori B.
Yang, Qiong
deStefano, Anita L.
de Quervain, Dominique J.F.
Srikanth, Velandai
Lahti, Jari
Grabe, Hans J.
Smith, Jennifer A.
Priebe, Lutz
Yu, Lei
Karbalai, Nazanin
Hayward, Caroline
Wilson, James F.
Campbell, Harry
Petrovic, Katja
Fornage, Myriam
Chauhan, Ganesh
Yeo, Robin
Boxall, Ruth
Becker, James
Stegle, Oliver
Mather, Karen A.
Chouraki, Vincent
Sun, Qi
Rose, Lynda M.
Resnick, Susan
Oldmeadow, Christopher
Kirin, Mirna
Wright, Alan F.
Jonsdottir, Maria K.
Au, Rhoda
Becker, Albert
Amin, Najaf
Nalls, Mike A.
Turner, Stephen T.
Kardia, Sharon L.R.
Oostra, Ben
Windham, Gwen
Coker, Laura H.
Zhao, Wei
Knopman, David S.
Heiss, Gerardo
Griswold, Michael E.
Gottesman, Rebecca F.
Vitart, Veronique
Hastie, Nicholas D.
Zgaga, Lina
Rudan, Igor
Polasek, Ozren
Holliday, Elizabeth G.
Schofield, Peter
Choi, Seung Hoan
Tanaka, Toshiko
An, Yang
Perry, Rodney T.
Kennedy, Richard E.
Sale, Michèle M.
Wang, Jing
Wadley, Virginia G.
Liewald, David C.
Ridker, Paul M.
Gow, Alan J.
Pattie, Alison
Starr, John M.
Porteous, David
Liu, Xuan
Thomson, Russell
Armstrong, Nicola J.
Eiriksdottir, Gudny
Assareh, Arezoo A.
Kochan, Nicole A.
Widen, Elisabeth
Palotie, Aarno
Hsieh, Yi-Chen
Eriksson, Johan G.
Vogler, Christian
van Swieten, John C.
Shulman, Joshua M.
Ferrucci, Luigi
Attia, John
Uitterlinden, Andre G.
Amouyel, Philippe
Dartigues, Jean-François
Amieva, Hélène
Räikkönen, Katri
Garcia, Melissa
Wolf, Philip A.
Hofman, Albert
Longstreth Jr, W.T.
Psaty, Bruce M.
Boerwinkle, Eric
DeJager, Philip L.
Sachdev, Perminder S.
Schmidt, Reinhold
Breteler, Monique M.B.
Teumer, Alexander
Lopez, Oscar L.
Cichon, Sven
Papassotiropoulos, Andreas
Bennett, David A.
Ikram, M. Arfan
Deary, Ian J.
van Duijn, Cornelia M.
Launer, Lenore
Fitzpatrick, Annette L.
Seshadri, Sudha
Mosley Jr, Thomas H.
for the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
Brown, Matthew A.
Title Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2014-11-25
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2014.08.027
Volume 77
Issue 8
Start page 749
End page 763
Total pages 15
Place of publication Philadelphia, PA United States
Publisher Elsevier
Language eng
Formatted 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.
Keyword Alzheimer disease
Verbal declarative memory
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
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Created: Tue, 31 Mar 2015, 21:34:09 EST by Kylie Hengst on behalf of UQ Diamantina Institute