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

S Debette; Carla Verbaas; J Bressler; Maaike Schuur; A Smith; JC Bis; G Davies; C Wolf; V Gudnason; LB Chibnik; Q Yang; AL DeStefano; DJF de Quervain; V Srikanth; J Lahti; HJ Grabe; JA Smith; L Priebe; L Yu; N Karbalai; C Hayward; JF Wilson; H Campbell; K Petrovic; M Fornage; G Chauhan; RB Yeo; R Boxall; J Becker; O Stegle; KA Mather; V Chouraki; Q Sun; LM Rose; S Resnick; C Oldmeadow; M Kirin; AF Wright; MK Jonsdottir; RD Au; A Becker; Najaf Amin; MA Nalls; ST Turner; SLR Kardia; Ben Oostra; G Windham; LH Coker; W Zhao; DS Knopman; G Heiss; ME Griswold; RF Gottesman; V Vitart; ND Hastie; L Zgaga; I Rudan; O Polasek; EG Holliday; P Schofield; SH Choi; T Tanaka; Y An; RT Perry; RE Kennedy; MM Sale; Johnny Wang; VG Wadley; DC Liewald; PM Ridker; AJ Gow; A Pattie; JM Starr; D Porteous; Nana Liu; R Thomson; NJ Armstrong; G Eiriksdottir; AA Assareh; NA Kochan; E Widen; A Palotie; YC (Yi-Chen) Hsieh; JG Eriksson; C Vogler; J.C. van Swieten; JM Shulman; A Beiser; J Rotter; CO Schmidt; W Hoffmann; MM Nothen; L Ferrucci; J Attia; André Uitterlinden; P Amouyel; JF Dartigues; H Amieva; K Raikkonen; M Garcia; PA Wolf; Bert Hofman; WT Longstreth; BM Psaty; E Boerwinkle; PL DeJager; PS Sachdev; R Schmidt; Monique Breteler; A Teumer; OL Lopez; S Cichon; DI Chasman; F Grodstein; B Muller-Myhsok; C Tzourio; A Papassotiropoulos; DA Bennett; Arfan Ikram; IJ Deary; Cornelia Duijn; L Launer; AL Fitzpatrick; S Seshadri; TH Mosley

doi:10.1016/j.biopsych.2014.08.027

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

S Debette, Carla Verbaas, J Bressler, Maaike Schuur, A Smith, JC Bis, G Davies, C Wolf, V Gudnason, LB Chibnik, Q Yang, AL DeStefano, DJF de Quervain, V Srikanth, J Lahti, HJ Grabe, JA Smith, L Priebe, L Yu, N KarbalaiC Hayward, JF Wilson, H Campbell, K Petrovic, M Fornage, G Chauhan, RB Yeo, R Boxall, J Becker, O Stegle, KA Mather, V Chouraki, Q Sun, LM Rose, S Resnick, C Oldmeadow, M Kirin, AF Wright, MK Jonsdottir, RD Au, A Becker, Najaf Amin, MA Nalls, ST Turner, SLR Kardia, Ben Oostra, G Windham, LH Coker, W Zhao, DS Knopman, G Heiss, ME Griswold, RF Gottesman, V Vitart, ND Hastie, L Zgaga, I Rudan, O Polasek, EG Holliday, P Schofield, SH Choi, T Tanaka, Y An, RT Perry, RE Kennedy, MM Sale, Johnny Wang, VG Wadley, DC Liewald, PM Ridker, AJ Gow, A Pattie, JM Starr, D Porteous, Nana Liu, R Thomson, NJ Armstrong, G Eiriksdottir, AA Assareh, NA Kochan, E Widen, A Palotie, YC (Yi-Chen) Hsieh, JG Eriksson, C Vogler, J.C. van Swieten, JM Shulman, A Beiser, J Rotter, CO Schmidt, W Hoffmann, MM Nothen, L Ferrucci, J Attia, André Uitterlinden, P Amouyel, JF Dartigues, H Amieva, K Raikkonen, M Garcia, PA Wolf, Bert Hofman, WT Longstreth, BM Psaty, E Boerwinkle, PL DeJager, PS Sachdev, R Schmidt, Monique Breteler, A Teumer, OL Lopez, S Cichon, DI Chasman, F Grodstein, B Muller-Myhsok, C Tzourio, A Papassotiropoulos, DA Bennett, Arfan Ikram, IJ Deary, Cornelia Duijn, L Launer, AL Fitzpatrick, S Seshadri, TH Mosley

Research output: Contribution to journal › Article › Academic › peer-review

62 Citations (Scopus)

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 x 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 = 55.7 x 10(-10)) and replication cohorts (p = 5.65 x 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 x 10(-8), and rs6813517 [SPOCK3], p = 2.58 x 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 similar to 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

Original language	Undefined/Unknown
Pages (from-to)	749-763
Number of pages	15
Journal	Biological Psychiatry
Volume	77
Issue number	8
DOIs	https://doi.org/10.1016/j.biopsych.2014.08.027
Publication status	Published - 2015

Research programs

EMC COEUR-09
EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-03-30-02

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.biopsych.2014.08.027

http://hdl.handle.net/1765/82577

Cite this

Debette, S., Verbaas, C., 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., ... Mosley, TH. (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), 749-763. https://doi.org/10.1016/j.biopsych.2014.08.027

@article{1ed9e16ba64e4702ad1c77e7c193c163,

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 x 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 = 55.7 x 10(-10)) and replication cohorts (p = 5.65 x 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 x 10(-8), and rs6813517 [SPOCK3], p = 2.58 x 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 similar to 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.",

author = "S Debette and Carla Verbaas and J Bressler and Maaike Schuur and A Smith and JC Bis and G Davies and C Wolf and V Gudnason and LB Chibnik and Q Yang and AL DeStefano and {de Quervain}, DJF and V Srikanth and J Lahti and HJ Grabe and JA Smith and L Priebe and L Yu and N Karbalai and C Hayward and JF Wilson and H Campbell and K Petrovic and M Fornage and G Chauhan and RB Yeo and R Boxall and J Becker and O Stegle and KA Mather and V Chouraki and Q Sun and LM Rose and S Resnick and C Oldmeadow and M Kirin and AF Wright and MK Jonsdottir and RD Au and A Becker and Najaf Amin and MA Nalls and ST Turner and SLR Kardia and Ben Oostra and G Windham and LH Coker and W Zhao and DS Knopman and G Heiss and ME Griswold and RF Gottesman and V Vitart and ND Hastie and L Zgaga and I Rudan and O Polasek and EG Holliday and P Schofield and SH Choi and T Tanaka and Y An and RT Perry and RE Kennedy and MM Sale and Johnny Wang and VG Wadley and DC Liewald and PM Ridker and AJ Gow and A Pattie and JM Starr and D Porteous and Nana Liu and R Thomson and NJ Armstrong and G Eiriksdottir and AA Assareh and NA Kochan and E Widen and A Palotie and Hsieh, {YC (Yi-Chen)} and JG Eriksson and C Vogler and {van Swieten}, J.C. and JM Shulman and A Beiser and J Rotter and CO Schmidt and W Hoffmann and MM Nothen and L Ferrucci and J Attia and Andr{\'e} Uitterlinden and P Amouyel and JF Dartigues and H Amieva and K Raikkonen and M Garcia and PA Wolf and Bert Hofman and WT Longstreth and BM Psaty and E Boerwinkle and PL DeJager and PS Sachdev and R Schmidt and Monique Breteler and A Teumer and OL Lopez and S Cichon and DI Chasman and F Grodstein and B Muller-Myhsok and C Tzourio and A Papassotiropoulos and DA Bennett and Arfan Ikram and IJ Deary and Cornelia Duijn and L Launer and AL Fitzpatrick and S Seshadri and TH Mosley",

year = "2015",

doi = "10.1016/j.biopsych.2014.08.027",

language = "Undefined/Unknown",

volume = "77",

pages = "749--763",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier Inc.",

number = "8",

}

Debette, S, Verbaas, C, 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, RB, 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, RD, 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, SH, 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, N, Thomson, R, Armstrong, NJ, Eiriksdottir, G, Assareh, AA, Kochan, NA, Widen, E, Palotie, A, Hsieh, YC, Eriksson, JG, Vogler, C, van Swieten, JC, Shulman, JM, Beiser, A, Rotter, J, Schmidt, CO, Hoffmann, W, Nothen, MM, Ferrucci, L, Attia, J, Uitterlinden, A, Amouyel, P, Dartigues, JF, Amieva, H, Raikkonen, K, Garcia, M, Wolf, PA, Hofman, B, Longstreth, WT, Psaty, BM, Boerwinkle, E, DeJager, PL, Sachdev, PS, Schmidt, R, Breteler, M, Teumer, A, Lopez, OL, Cichon, S, Chasman, DI, Grodstein, F, Muller-Myhsok, B, Tzourio, C, Papassotiropoulos, A, Bennett, DA, Ikram, A, Deary, IJ, Duijn, C, Launer, L, Fitzpatrick, AL, Seshadri, S & Mosley, TH 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, vol. 77, no. 8, pp. 749-763. https://doi.org/10.1016/j.biopsych.2014.08.027

TY - JOUR

T1 - Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

AU - Debette, S

AU - Verbaas, Carla

AU - Bressler, J

AU - Schuur, Maaike

AU - Smith, A

AU - Bis, JC

AU - Davies, G

AU - Wolf, C

AU - Gudnason, V

AU - Chibnik, LB

AU - Yang, Q

AU - DeStefano, AL

AU - de Quervain, DJF

AU - Srikanth, V

AU - Lahti, J

AU - Grabe, HJ

AU - Smith, JA

AU - Priebe, L

AU - Yu, L

AU - Karbalai, N

AU - Hayward, C

AU - Wilson, JF

AU - Campbell, H

AU - Petrovic, K

AU - Fornage, M

AU - Chauhan, G

AU - Yeo, RB

AU - Boxall, R

AU - Becker, J

AU - Stegle, O

AU - Mather, KA

AU - Chouraki, V

AU - Sun, Q

AU - Rose, LM

AU - Resnick, S

AU - Oldmeadow, C

AU - Kirin, M

AU - Wright, AF

AU - Jonsdottir, MK

AU - Au, RD

AU - Becker, A

AU - Amin, Najaf

AU - Nalls, MA

AU - Turner, ST

AU - Kardia, SLR

AU - Oostra, Ben

AU - Windham, G

AU - Coker, LH

AU - Zhao, W

AU - Knopman, DS

AU - Heiss, G

AU - Griswold, ME

AU - Gottesman, RF

AU - Vitart, V

AU - Hastie, ND

AU - Zgaga, L

AU - Rudan, I

AU - Polasek, O

AU - Holliday, EG

AU - Schofield, P

AU - Choi, SH

AU - Tanaka, T

AU - An, Y

AU - Perry, RT

AU - Kennedy, RE

AU - Sale, MM

AU - Wang, Johnny

AU - Wadley, VG

AU - Liewald, DC

AU - Ridker, PM

AU - Gow, AJ

AU - Pattie, A

AU - Starr, JM

AU - Porteous, D

AU - Liu, Nana

AU - Thomson, R

AU - Armstrong, NJ

AU - Eiriksdottir, G

AU - Assareh, AA

AU - Kochan, NA

AU - Widen, E

AU - Palotie, A

AU - Hsieh, YC (Yi-Chen)

AU - Eriksson, JG

AU - Vogler, C

AU - van Swieten, J.C.

AU - Shulman, JM

AU - Beiser, A

AU - Rotter, J

AU - Schmidt, CO

AU - Hoffmann, W

AU - Nothen, MM

AU - Ferrucci, L

AU - Attia, J

AU - Uitterlinden, André

AU - Amouyel, P

AU - Dartigues, JF

AU - Amieva, H

AU - Raikkonen, K

AU - Garcia, M

AU - Wolf, PA

AU - Hofman, Bert

AU - Longstreth, WT

AU - Psaty, BM

AU - Boerwinkle, E

AU - DeJager, PL

AU - Sachdev, PS

AU - Schmidt, R

AU - Breteler, Monique

AU - Teumer, A

AU - Lopez, OL

AU - Cichon, S

AU - Chasman, DI

AU - Grodstein, F

AU - Muller-Myhsok, B

AU - Tzourio, C

AU - Papassotiropoulos, A

AU - Bennett, DA

AU - Ikram, Arfan

AU - Deary, IJ

AU - Duijn, Cornelia

AU - Launer, L

AU - Fitzpatrick, AL

AU - Seshadri, S

AU - Mosley, TH

PY - 2015

Y1 - 2015

N2 - 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 x 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 = 55.7 x 10(-10)) and replication cohorts (p = 5.65 x 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 x 10(-8), and rs6813517 [SPOCK3], p = 2.58 x 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 similar to 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

AB - 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 x 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 = 55.7 x 10(-10)) and replication cohorts (p = 5.65 x 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 x 10(-8), and rs6813517 [SPOCK3], p = 2.58 x 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 similar to 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

U2 - 10.1016/j.biopsych.2014.08.027

DO - 10.1016/j.biopsych.2014.08.027

M3 - Article

C2 - 25648963

SN - 0006-3223

VL - 77

SP - 749

EP - 763

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 8

ER -