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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.

Friday,2015-04-17 14:08 America/Los_Angeles — zdrager
TitleGenome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.
Publication TypeJournal Article
Year of Publication2015
AuthorsDebette, S, Verbaas, CAIbrahim, Bressler, J, Schuur, M, Smith, A, Bis, JC, Davies, G, Wolf, C, Gudnason, V, Chibnik, LB, Yang, Q, DeStefano, AL, de Quervain, DJF, Srikanth, V, Lahti, J, Grabe, HJ, Smith, JA, Priebe, L, Yu, L, Karbalai, N, Hayward, C, Wilson, JF, Campbell, H, Petrovic, K, Fornage, M, Chauhan, G, Yeo, R, Boxall, R, Becker, J, Stegle, O, Mather, KA, Chouraki, V, Sun, Q, Rose, LM, Resnick, S, Oldmeadow, C, Kirin, M, Wright, AF, Jonsdottir, MK, Au, R, Becker, A, Amin, N, Nalls, MA, Turner, ST, Kardia, SLR, Oostra, B, Windham, G, Coker, LH, Zhao, W, Knopman, DS, Heiss, G, Griswold, ME, Gottesman, RF, Vitart, V, Hastie, ND, Zgaga, L, Rudan, I, Polasek, O, Holliday, EG, Schofield, P, Choi, SHoan, Tanaka, T, An, Y, Perry, RT, Kennedy, RE, Sale, MM, Wang, J, Wadley, VG, Liewald, DC, Ridker, PM, Gow, AJ, Pattie, A, Starr, JM, Porteous, D, Liu, X, Thomson, R, Armstrong, NJ, Eiriksdottir, G, Assareh, AA, Kochan, NA, Widen, E, Palotie, A, Hsieh, Y-C, Eriksson, JG, Vogler, C, van Swieten, JC, Shulman, JM, Beiser, A, Rotter, J, Schmidt, CO, Hoffmann, W, Nöthen, MM, Ferrucci, L, Attia, J, Uitterlinden, AG, Amouyel, P, Dartigues, J-F, Amieva, H, Räikkönen, K, Garcia, M, Wolf, PA, Hofman, A, Longstreth, WT, Psaty, BM, Boerwinkle, E, DeJager, PL, Sachdev, PS, Schmidt, R, Breteler, MMB, Teumer, A, Lopez, OL, Cichon, S, Chasman, DI, Grodstein, F, Müller-Myhsok, B, Tzourio, C, Papassotiropoulos, A, Bennett, DA, Ikram, AM, Deary, IJ, van Duijn, CM, Launer, L, Fitzpatrick, AL, Seshadri, S, Mosley, TH
Corporate/Institutional AuthorsCohorts for Heart and Aging Research in Genomic Epidemiology Consortium,
JournalBiol Psychiatry
Volume77
Issue8
Pagination749-63
Date Published2015 Apr 15
ISSN1873-2402
KeywordsAged, Aged, 80 and over, Aging, Apolipoproteins E, Claudin-5, Cohort Studies, Female, Genome-Wide Association Study, Genotype, Humans, Male, Memory Disorders, Middle Aged, Polymorphism, Single Nucleotide, Proteins, Proteoglycans, Regression Analysis, Sulfotransferases, Verbal Learning
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1016/j.biopsych.2014.08.027
Alternate JournalBiol. Psychiatry
PubMed ID25648963
PubMed Central IDPMC4513651
Grant List5UO1CA098233 / CA / NCI NIH HHS / United States
AG031287 / AG / NIA NIH HHS / United States
AG033193 / AG / NIA NIH HHS / United States
AG08122 / AG / NIA NIH HHS / United States
AG16495 / AG / NIA NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
CA047988 / CA / NCI NIH HHS / United States
CA134958 / CA / NCI NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
CA50385 / CA / NCI NIH HHS / United States
CA55075 / CA / NCI NIH HHS / United States
CA65725 / CA / NCI NIH HHS / United States
CA67262 / CA / NCI NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
CZB/4/505 / / Chief Scientist Office / United Kingdom
CZB/4/710 / / Chief Scientist Office / United Kingdom
DK058845 / DK / NIDDK NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
DK070756 / DK / NIDDK NIH HHS / United States
ETM/55 / / Chief Scientist Office / United Kingdom
EY015473 / EY / NEI NIH HHS / United States
EY09611 / EY / NEI NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
HG004728 / HG / NHGRI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
HHSN268200800007C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL043851 / HL / NHLBI NIH HHS / United States
HL054457 / HL / NHLBI NIH HHS / United States
HL054464 / HL / NHLBI NIH HHS / United States
HL054481 / HL / NHLBI NIH HHS / United States
HL071917 / HL / NHLBI NIH HHS / United States
HL080467 / HL / NHLBI NIH HHS / United States
HL34594 / HL / NHLBI NIH HHS / United States
HL35464 / HL / NHLBI NIH HHS / United States
HL87660 / HL / NHLBI NIH HHS / United States
K08AG34290 / AG / NIA NIH HHS / United States
K25AG41906 / AG / NIA NIH HHS / United States
K99HL098459 / HL / NHLBI NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
N01-AG-12100 / AG / NIA NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
NS041558 / NS / NINDS NIH HHS / United States
NS17950 / NS / NINDS NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
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R01 HL120393 / HL / NHLBI NIH HHS / United States
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R01HL59367 / HL / NHLBI NIH HHS / United States
R01HL70825 / HL / NHLBI NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
S18386 / / Biotechnology and Biological Sciences Research Council / United Kingdom
U01 AG049505 / AG / NIA NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 NS041588 / NS / NINDS NIH HHS / United States
U01HG004399 / HG / NHGRI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
WT089062 / / Wellcome Trust / United Kingdom
Z01 AG007270-08 / / Intramural NIH HHS / United States
Z01 AG007380-02 / / Intramural NIH HHS / United States
/ / Biotechnology and Biological Sciences Research Council / United Kingdom

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