Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Jari Lahti; Samuli Tuominen; Qiong Yang; Giulio Pergola; Shahzad Ahmad; Najaf Amin; Nicola J Armstrong; Alexa Beiser; Katharina Bey; Joshua C Bis; Eric Boerwinkle; Jan Bressler; Archie Campbell; Harry Campbell; Qiang Chen; Janie Corley; Simon R Cox; Gail Davies; Philip L De Jager; Eske M Derks; Jessica D Faul; Annette L Fitzpatrick; Alison E Fohner; Ian Ford; Myriam Fornage; Zachary Gerring; Hans J Grabe; Francine Grodstein; Vilmundur Gudnason; Eleanor Simonsick; Elizabeth G Holliday; Peter K Joshi; Eero Kajantie; Jaakko Kaprio; Pauliina Karell; Luca Kleineidam; Maria J Knol; Nicole A Kochan; John B Kwok; Markus Leber; Max Lam; Teresa Lee; Shuo Li; Anu Loukola; Tobias Luck; Riccardo E Marioni; Karen A Mather; Sarah Medland; Saira S Mirza; Mike A Nalls; Kwangsik Nho; Adrienne O'Donnell; Christopher Oldmeadow; Jodie Painter; Alison Pattie; Simone Reppermund; Shannon L Risacher; Richard J Rose; Vijay Sadashivaiah; Markus Scholz; Claudia L Satizabal; Peter W Schofield; Katharina E Schraut; Rodney J Scott; Jeannette Simino; Albert V Smith; Jennifer A Smith; David J Stott; Ida Surakka; Alexander Teumer; Anbupalam Thalamuthu; Stella Trompet; Stephen T Turner; Sven J van der Lee; Arno Villringer; Uwe Völker; Robert S Wilson; Katharina Wittfeld; Eero Vuoksimaa; Rui Xia; Kristine Yaffe; Lei Yu; Habil Zare; Wei Zhao; David Ames; John Attia; David A Bennett; Henry Brodaty; Daniel I Chasman; Aaron L Goldman; Caroline Hayward; M Arfan Ikram; J Wouter Jukema; Sharon L R Kardia; Todd Lencz; Markus Loeffler; Venkata S Mattay; Aarno Palotie; Bruce M Psaty; Alfredo Ramirez; Paul M Ridker; Steffi G Riedel-Heller; Perminder S Sachdev; Andrew J Saykin; Martin Scherer; Peter R Schofield; Stephen Sidney; John M Starr; Julian Trollor; William Ulrich; Michael Wagner; David R Weir; James F Wilson; Margaret J Wright; Daniel R Weinberger; Stephanie Debette; Johan G Eriksson; Thomas H Mosley; Lenore J Launer; Cornelia M van Duijn; Ian J Deary; Sudha Seshadri; Katri Räikkönen

doi:10.1038/s41380-022-01710-8

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Jari Lahti, Samuli Tuominen, Qiong Yang, Giulio Pergola, Shahzad Ahmad, Najaf Amin, Nicola J Armstrong, Alexa Beiser, Katharina Bey, Joshua C Bis, Eric Boerwinkle, Jan Bressler, Archie Campbell, Harry Campbell, Qiang Chen, Janie Corley, Simon R Cox, Gail Davies, Philip L De Jager, Eske M DerksJessica D Faul, Annette L Fitzpatrick, Alison E Fohner, Ian Ford, Myriam Fornage, Zachary Gerring, Hans J Grabe, Francine Grodstein, Vilmundur Gudnason, Eleanor Simonsick, Elizabeth G Holliday, Peter K Joshi, Eero Kajantie, Jaakko Kaprio, Pauliina Karell, Luca Kleineidam, Maria J Knol, Nicole A Kochan, John B Kwok, Markus Leber, Max Lam, Teresa Lee, Shuo Li, Anu Loukola, Tobias Luck, Riccardo E Marioni, Karen A Mather, Sarah Medland, Saira S Mirza, Mike A Nalls, Kwangsik Nho, Adrienne O'Donnell, Christopher Oldmeadow, Jodie Painter, Alison Pattie, Simone Reppermund, Shannon L Risacher, Richard J Rose, Vijay Sadashivaiah, Markus Scholz, Claudia L Satizabal, Peter W Schofield, Katharina E Schraut, Rodney J Scott, Jeannette Simino, Albert V Smith, Jennifer A Smith, David J Stott, Ida Surakka, Alexander Teumer, Anbupalam Thalamuthu, Stella Trompet, Stephen T Turner, Sven J van der Lee, Arno Villringer, Uwe Völker, Robert S Wilson, Katharina Wittfeld, Eero Vuoksimaa, Rui Xia, Kristine Yaffe, Lei Yu, Habil Zare, Wei Zhao, David Ames, John Attia, David A Bennett, Henry Brodaty, Daniel I Chasman, Aaron L Goldman, Caroline Hayward, M Arfan Ikram, J Wouter Jukema, Sharon L R Kardia, Todd Lencz, Markus Loeffler, Venkata S Mattay, Aarno Palotie, Bruce M Psaty, Alfredo Ramirez, Paul M Ridker, Steffi G Riedel-Heller, Perminder S Sachdev, Andrew J Saykin, Martin Scherer, Peter R Schofield, Stephen Sidney, John M Starr, Julian Trollor, William Ulrich, Michael Wagner, David R Weir, James F Wilson, Margaret J Wright, Daniel R Weinberger, Stephanie Debette, Johan G Eriksson, Thomas H Mosley, Lenore J Launer, Cornelia M van Duijn, Ian J Deary, Sudha Seshadri, Katri Räikkönen

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

Abstract / Description of output

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Original language	English
Pages (from-to)	4419-4431
Journal	Molecular Psychiatry
Volume	27
Issue number	11
Early online date	16 Aug 2022
DOIs	https://doi.org/10.1038/s41380-022-01710-8
Publication status	E-pub ahead of print - 16 Aug 2022

Keywords / Materials (for Non-textual outputs)

Brain
Learning
Memory, Short-Term/physiology
Multifactorial Inheritance
Verbal Learning

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10.1038/s41380-022-01710-8Licence: Creative Commons: Attribution (CC-BY)

s41380-022-01710-8Final published version, 3.48 MBLicence: Creative Commons: Attribution (CC-BY)

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Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N. J., Beiser, A., Bey, K., Bis, J. C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S. R., Davies, G., De Jager, P. L., ... Räikkönen, K. (2022). Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning. Molecular Psychiatry, 27(11), 4419-4431. Advance online publication. https://doi.org/10.1038/s41380-022-01710-8

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title = "Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning",

abstract = "Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.",

keywords = "Brain, Learning, Memory, Short-Term/physiology, Multifactorial Inheritance, Verbal Learning",

author = "Jari Lahti and Samuli Tuominen and Qiong Yang and Giulio Pergola and Shahzad Ahmad and Najaf Amin and Armstrong, {Nicola J} and Alexa Beiser and Katharina Bey and Bis, {Joshua C} and Eric Boerwinkle and Jan Bressler and Archie Campbell and Harry Campbell and Qiang Chen and Janie Corley and Cox, {Simon R} and Gail Davies and {De Jager}, {Philip L} and Derks, {Eske M} and Faul, {Jessica D} and Fitzpatrick, {Annette L} and Fohner, {Alison E} and Ian Ford and Myriam Fornage and Zachary Gerring and Grabe, {Hans J} and Francine Grodstein and Vilmundur Gudnason and Eleanor Simonsick and Holliday, {Elizabeth G} and Joshi, {Peter K} and Eero Kajantie and Jaakko Kaprio and Pauliina Karell and Luca Kleineidam and Knol, {Maria J} and Kochan, {Nicole A} and Kwok, {John B} and Markus Leber and Max Lam and Teresa Lee and Shuo Li and Anu Loukola and Tobias Luck and Marioni, {Riccardo E} and Mather, {Karen A} and Sarah Medland and Mirza, {Saira S} and Nalls, {Mike A} and Kwangsik Nho and Adrienne O'Donnell and Christopher Oldmeadow and Jodie Painter and Alison Pattie and Simone Reppermund and Risacher, {Shannon L} and Rose, {Richard J} and Vijay Sadashivaiah and Markus Scholz and Satizabal, {Claudia L} and Schofield, {Peter W} and Schraut, {Katharina E} and Scott, {Rodney J} and Jeannette Simino and Smith, {Albert V} and Smith, {Jennifer A} and Stott, {David J} and Ida Surakka and Alexander Teumer and Anbupalam Thalamuthu and Stella Trompet and Turner, {Stephen T} and {van der Lee}, {Sven J} and Arno Villringer and Uwe V{\"o}lker and Wilson, {Robert S} and Katharina Wittfeld and Eero Vuoksimaa and Rui Xia and Kristine Yaffe and Lei Yu and Habil Zare and Wei Zhao and David Ames and John Attia and Bennett, {David A} and Henry Brodaty and Chasman, {Daniel I} and Goldman, {Aaron L} and Caroline Hayward and Ikram, {M Arfan} and Jukema, {J Wouter} and Kardia, {Sharon L R} and Todd Lencz and Markus Loeffler and Mattay, {Venkata S} and Aarno Palotie and Psaty, {Bruce M} and Alfredo Ramirez and Ridker, {Paul M} and Riedel-Heller, {Steffi G} and Sachdev, {Perminder S} and Saykin, {Andrew J} and Martin Scherer and Schofield, {Peter R} and Stephen Sidney and Starr, {John M} and Julian Trollor and William Ulrich and Michael Wagner and Weir, {David R} and Wilson, {James F} and Wright, {Margaret J} and Weinberger, {Daniel R} and Stephanie Debette and Eriksson, {Johan G} and Mosley, {Thomas H} and Launer, {Lenore J} and {van Duijn}, {Cornelia M} and Deary, {Ian J} and Sudha Seshadri and Katri R{\"a}ikk{\"o}nen",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = aug,

day = "16",

doi = "10.1038/s41380-022-01710-8",

language = "English",

volume = "27",

pages = "4419--4431",

journal = "Molecular Psychiatry",

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number = "11",

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Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A , Campbell, H, Chen, Q, Corley, J , Cox, SR , Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Völker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S & Räikkönen, K 2022, 'Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning', Molecular Psychiatry, vol. 27, no. 11, pp. 4419-4431. https://doi.org/10.1038/s41380-022-01710-8

TY - JOUR

T1 - Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

AU - Lahti, Jari

AU - Tuominen, Samuli

AU - Yang, Qiong

AU - Pergola, Giulio

AU - Ahmad, Shahzad

AU - Amin, Najaf

AU - Armstrong, Nicola J

AU - Beiser, Alexa

AU - Bey, Katharina

AU - Bis, Joshua C

AU - Boerwinkle, Eric

AU - Bressler, Jan

AU - Campbell, Archie

AU - Campbell, Harry

AU - Chen, Qiang

AU - Corley, Janie

AU - Cox, Simon R

AU - Davies, Gail

AU - De Jager, Philip L

AU - Derks, Eske M

AU - Faul, Jessica D

AU - Fitzpatrick, Annette L

AU - Fohner, Alison E

AU - Ford, Ian

AU - Fornage, Myriam

AU - Gerring, Zachary

AU - Grabe, Hans J

AU - Grodstein, Francine

AU - Gudnason, Vilmundur

AU - Simonsick, Eleanor

AU - Holliday, Elizabeth G

AU - Joshi, Peter K

AU - Kajantie, Eero

AU - Kaprio, Jaakko

AU - Karell, Pauliina

AU - Kleineidam, Luca

AU - Knol, Maria J

AU - Kochan, Nicole A

AU - Kwok, John B

AU - Leber, Markus

AU - Lam, Max

AU - Lee, Teresa

AU - Li, Shuo

AU - Loukola, Anu

AU - Luck, Tobias

AU - Marioni, Riccardo E

AU - Mather, Karen A

AU - Medland, Sarah

AU - Mirza, Saira S

AU - Nalls, Mike A

AU - Nho, Kwangsik

AU - O'Donnell, Adrienne

AU - Oldmeadow, Christopher

AU - Painter, Jodie

AU - Pattie, Alison

AU - Reppermund, Simone

AU - Risacher, Shannon L

AU - Rose, Richard J

AU - Sadashivaiah, Vijay

AU - Scholz, Markus

AU - Satizabal, Claudia L

AU - Schofield, Peter W

AU - Schraut, Katharina E

AU - Scott, Rodney J

AU - Simino, Jeannette

AU - Smith, Albert V

AU - Smith, Jennifer A

AU - Stott, David J

AU - Surakka, Ida

AU - Teumer, Alexander

AU - Thalamuthu, Anbupalam

AU - Trompet, Stella

AU - Turner, Stephen T

AU - van der Lee, Sven J

AU - Villringer, Arno

AU - Völker, Uwe

AU - Wilson, Robert S

AU - Wittfeld, Katharina

AU - Vuoksimaa, Eero

AU - Xia, Rui

AU - Yaffe, Kristine

AU - Yu, Lei

AU - Zare, Habil

AU - Zhao, Wei

AU - Ames, David

AU - Attia, John

AU - Bennett, David A

AU - Brodaty, Henry

AU - Chasman, Daniel I

AU - Goldman, Aaron L

AU - Hayward, Caroline

AU - Ikram, M Arfan

AU - Jukema, J Wouter

AU - Kardia, Sharon L R

AU - Lencz, Todd

AU - Loeffler, Markus

AU - Mattay, Venkata S

AU - Palotie, Aarno

AU - Psaty, Bruce M

AU - Ramirez, Alfredo

AU - Ridker, Paul M

AU - Riedel-Heller, Steffi G

AU - Sachdev, Perminder S

AU - Saykin, Andrew J

AU - Scherer, Martin

AU - Schofield, Peter R

AU - Sidney, Stephen

AU - Starr, John M

AU - Trollor, Julian

AU - Ulrich, William

AU - Wagner, Michael

AU - Weir, David R

AU - Wilson, James F

AU - Wright, Margaret J

AU - Weinberger, Daniel R

AU - Debette, Stephanie

AU - Eriksson, Johan G

AU - Mosley, Thomas H

AU - Launer, Lenore J

AU - van Duijn, Cornelia M

AU - Deary, Ian J

AU - Seshadri, Sudha

AU - Räikkönen, Katri

PY - 2022/8/16

Y1 - 2022/8/16

N2 - Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

AB - Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

KW - Brain

KW - Learning

KW - Memory, Short-Term/physiology

KW - Multifactorial Inheritance

KW - Verbal Learning

U2 - 10.1038/s41380-022-01710-8

DO - 10.1038/s41380-022-01710-8

M3 - Article

C2 - 35974141

SN - 1359-4184

VL - 27

SP - 4419

EP - 4431

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 11

ER -

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

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Keywords / Materials (for Non-textual outputs)

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