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GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Authors :
Igor Rudan
Daniel I. Chasman
Helena Schmidt
Stefan Herms
Sharon L.R. Kardia
Oliver Stegle
Alison Pattie
Jenna Price
Gerardo Heiss
Karen A. Mather
L. J. Launer
Johan G. Eriksson
Christopher Oldmeadow
Ian Ford
Saira Saeed Mirza
Alan F. Wright
Ozren Polasek
Joshua M. Shulman
Maria K. Jonsdottir
André G. Uitterlinden
Rodney J. Scott
Kurt Lohman
Anita L. DeStefano
Peter W. Schofield
Perminder S. Sachdev
Stefania Bandinelli
Johan Wouter Jukema
John M. Starr
Rudolf S N Fehrmann
Y. C. Hsieh
William M. Meeks
Paul M. Ridker
R.G.J. Westendorp
Le Yu
J. C. van Swieten
Vilmundur Gudnason
Myriam Fornage
Melissa Garcia
Carla A. Ibrahim-Verbaas
James F. Wilson
Jean-Charles Lambert
Qiong Yang
Laura H. Coker
Stella Trompet
Lina Zgaga
Jennifer A. Smith
David J. Llewellyn
Nicole A. Kochan
Ben A. Oostra
Katja Petrovic
Peter Hoffmann
Qi Sun
James T. Becker
Najaf Amin
Vincent Chouraki
Brendan M. Buckley
D C Liewald
Jun Ding
Christiane Wolf
P. L. DeJager
Reinhold Schmidt
Chloe Fawns-Ritchie
Stéphanie Debette
Jing Wang
J. C. Bis
Nicola J. Armstrong
David J. Stott
Albert Hofman
Nazanin Karbalai
G. Eiriksdottir
Luke C. Pilling
D. S. Knopman
Maaike Schuur
Alexa S. Beiser
Annette L. Fitzpatrick
David A. Bennett
Aarno Palotie
Lude Franke
Sven Cichon
Mirna Kirin
Markus M. Nöthen
Thomas H. Mosley
Lynda M. Rose
Alan J. Gow
Caroline Hayward
Lori B. Chibnik
Ian J. Deary
Albert V. Smith
Jan Bressler
T.B. Harris
Stephen T. Turner
David J. Porteous
C M van Duijn
M. A. Ikram
Elizabeth G. Holliday
Mike A. Nalls
Luigi Ferrucci
Sudha Seshadri
Francine Grodstein
Marlene C. W. Stewart
Philip A. Wolf
Alexander Teumer
P.E. Slagboom
Jerome I. Rotter
Blair H. Smith
Juha Karjalainen
Susan M. Resnick
A.J.M. de Craen
Toshiko Tanaka
Alan D. Penman
Hans-Jörgen Grabe
Gary Davies
Oscar L. Lopez
Yongmei Liu
Kristine Yaffe
Veronique Vitart
Stela McLachlan
Katri Räikkönen
Rebecca F. Gottesman
Rhoda Au
Lynne J. Hocking
Carsten Oliver Schmidt
John Attia
Bruce M. Psaty
Wei Zhao
Jari Lahti
Epidemiology
Neurology
Clinical Genetics
Internal Medicine
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Human genetics
Amsterdam Neuroscience - Neurodegeneration
Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Stem Cell Aging Leukemia and Lymphoma (SALL)
Source :
Molecular Psychiatry, 21(2), 189-197. Nature Publishing Group, Molecular Psychiatry, 21(2), 189-197, Ibrahim-Verbaas, C A, Bressler, J, Debette, S, Schuur, M, Smith, A V, Bis, J C, Davies, G, Trompet, S, Smith, J A, Wolf, C, Chibnik, L B, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, D J, Schmidt, C O, Mather, K A, Chouraki, V, Sun, Q, Resnick, S M, Rose, L M, Oldmeadow, C, Stewart, M, Smith, B H, Gudnason, V, Yang, Q, Mirza, S S, Jukema, J W, deJager, P L, Harris, T B, Liewald, D, Amin, N, Gow, A J, Pattie, A, Starr, J M, McLachlan, S, Porteous, D J, Price, J F, Rudan, I, Hayward, C, Wright, A F & Wilson, J F & Deary, I 2016, ' GWAS for executive function and processing speed suggests involvement of the CADM2 gene ', Molecular Psychiatry, vol. 21, pp. 189-197 . https://doi.org/10.1038/mp.2015.37, Ibrahim-Verbaas, CA; Bressler, J; Debette, S; Schuur, M; Smith, AV; Bis, JC; et al.(2016). GWAS for executive function and processing speed suggests involvement of the CADM2 gene. MOLECULAR PSYCHIATRY, 21(2), 189-197. doi: 10.1038/mp.2015.37. UCLA: Retrieved from: http://www.escholarship.org/uc/item/7d8152n1, Molecular psychiatry 21(2), 189-197 (2015). doi:10.1038/mp.2015.37, Neurology Working Group of the CHARGE Consortium 2016, ' GWAS for executive function and processing speed suggests involvement of the CADM2 gene ', Molecular Psychiatry, vol. 21, no. 2, pp. 189-197 . https://doi.org/10.1038/mp.2015.37, Molecular psychiatry 21, 189–197 (2016). doi:10.1038/mp.2015.37
Publication Year :
2016

Abstract

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed. National Foundation for Alzheimer's disease and related disorders Institut Pasteur de Lille Centre National de Genotypage Inserm FRC (fondation pour la recherche sur le cerveau) Rotary LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease) MEDIALZ Project - ERDF (European Regional Development Fund) 11001003 Conseil Regional Nord Pas de Calais Fondation pour la Recherche Medicale Caisse Nationale Maladie des Travailleurs Salaries Direction Generale de la Sante MGEN Institut de la Longevite Agence Francaise de Securite Sanitaire des Produits de Sante Aquitaine and Bourgogne Regional Councils Fondation de France joint French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' program Eisai Wellcome Trust British Heart Foundation Chief Scientist Office of the Scottish Executive NIA N01-AG-12100 National Heart, Lung and Blood Institute Contracts HHSN268201100005C HHSN268201100006C HHSN268201100007C HHSN268201100008C HHSN268201100009C HHSN268201100010C HHSN268201100011C HHSN268201100012C R01HL70825 R01HL087641 R01HL59367 R01HL086694 National Human Genome Research Institute U01HG004402 NIH Roadmap for Medical Research Austrian Science Fond (FWF) P20545-P05 P13180 Intramural Research Program of the NIH, National Institute on Aging NHLBI HHSN268201200036C HHSN268200800007C N01HC55222 N01HC85079 N01HC85080 N01HC85081 N01HC85082 N01HC85083 N01HC850863 U01HL080295 R01HL087652 R01HL105756 R01HL103612 R01HL120393 National Institute of Neurological Disorders and Stroke (NINDS) National Institute on Aging (NIA) R01AG023629 R01AG15928 R01AG20098 R01AG027058 National Center for Advancing Translational Sciences CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) DK063491 Medical Research Council (UK) European Commission Framework 6 project EUROSPAN LSHG-CT-2006-018947 Republic of Croatia Ministry of Science, Education and Sports 108-1080315-0302 Netherlands Organization for Scientific Research (NWO) Internationale Stichting Alzheimer Onderzoek (ISAO) Hersenstichting Nederland (HSN) Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI) Russian Foundation for Basic Research (RFBR) National Heart, Lung and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc N02-HL-6-4278 U01 HL096917 R01 HL093029 Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine Boston Medical Center National Institute of Neurological Disorders and Stroke NS17950 National Institute of Aging U01 AG049505 AG033193 AG008122 AG16495 Agence National de la Recherche Leducq Foundation National Heart, Lung and Blood Institute HL054464 HL054457 HL054481 HL071917 HL87660 HL043851 HL080467 National Institute of Neurological Disorders and Stroke of the National Institutes of Health NS041558 Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 Scottish Funding Council HR03006 Academy of Finland Finnish Diabetes Research Society Folkhalsan Research Foundation Novo Nordisk Foundation Finska Lakaresallskapet Signe and Ane Gyllenberg Foundation University of Helsinki Ministry of Education Ahokas Foundation Emil Aaltonen Foundation Juho Vainio Foundation Wellcome Trust WT089062 University of Newcastle's Strategic Initiative Fund Vincent Fairfax Family Foundation Hunter Medical Research Institute Italian Ministry of Health ICS 110.1RS97.71 US National Institute on Aging N01[AG]916413 N01[AG]821336 263 MD 9164 13 263 MD 821336 Intramural Research Program, National Institute on Aging, National Institutes of Health BBSRC Royal Society Chief Scientist Office of the Scottish Government Research Into Ageing UK Biotechnology and Biological Sciences Research Council (BBSRC) Engineering and Physical Sciences Research Council (EPSRC) Economic and Social Research Council (ESRC) MRC NHMRC 401184 Australian National Health & Medical Research Council 350833 568969 Capacity Building Grant 568940 NHMRC Project 525453 National Institutes of Health CA87969 CA49449 HL34594 U01HG004399 DK058845 CA65725 CA67262 CA50385 5UO1CA098233 EY09611 EY015473 HG004728 HL35464 CA55075 CA134958 DK070756 MRC Human Genetics Unit Arthritis Research UK European Union LSHG-CT-2006-018947 Bristol-Myers Squibb Netherlands Heart Foundation 2001 D 032 European commission 223004 Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) 050-060-810 Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project 050-060-810 Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases 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Details

Language :
English
ISSN :
13594184
Volume :
21
Issue :
2
Database :
OpenAIRE
Journal :
Molecular Psychiatry
Accession number :
edsair.doi.dedup.....dbf11a1a3e166a98f0a244478f602cbf
Full Text :
https://doi.org/10.1038/mp.2015.37