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@ARTICLE{IbrahimVerbaas:200955,
author = {Ibrahim-Verbaas, C. A. and Bressler, J. and Debette, S. and
Schuur, M. and Smith, A. V. and Bis, J. C. and Davies, G.
and Trompet, S. and Smith, J. A. and Wolf, C. and Chibnik,
L. B. and Liu, Y. and Vitart, V. and Kirin, M. and Petrovic,
K. and Polasek, O. and Zgaga, L. and Fawns-Ritchie, C. and
Hoffmann, P. and Karjalainen, J. and Lahti, J. and
Llewellyn, D. J. and Schmidt, C. O. and Mather, K. A. and
Chouraki, V. and Sun, Q. and Resnick, S. M. and Rose, L. M.
and Oldmeadow, C. and Stewart, M. and Smith, B. H. and
Gudnason, V. and Yang, Q. and Mirza, S. S. and Jukema, J. W.
and deJager, P. L. and Harris, T. B. and Liewald, D. C. and
Amin, N. and Coker, L. H. and Stegle, O. and Lopez, O. L.
and Schmidt, R. and Teumer, A. and Ford, I. and Karbalai, N.
and Becker, J. T. and Jonsdottir, M. K. and Au, R. and
Fehrmann, R. S. N. and Herms, S. and Nalls, M. and Zhao, W.
and Turner, S. T. and Yaffe, K. and Lohman, K. and van
Swieten, J. C. and Kardia, S. L. R. and Knopman, D. S. and
Meeks, W. M. and Heiss, G. and Holliday, E. G. and
Schofield, P. W. and Tanaka, T. and Stott, D. J. and Wang,
J. and Ridker, P. and Gow, A. J. and Pattie, A. and Starr,
J. M. and Hocking, L. J. and Armstrong, N. J. and McLachlan,
S. and Shulman, J. M. and Pilling, L. C. and Eiriksdottir,
G. and Scott, R. J. and Kochan, N. A. and Palotie, A. and
Hsieh, Y-C and Eriksson, J. G. and Penman, A. and Gottesman,
R. F. and Oostra, B. A. and Yu, L. and DeStefano, A. L. and
Beiser, A. and Garcia, M. and Rotter, J. I. and Nöthen, M.
M. and Hofman, A. and Slagboom, P. E. and Westendorp, R. G.
J. and Buckley, B. M. and Wolf, P. A. and Uitterlinden, A.
G. and Psaty, B. M. and Grabe, H. J. and Bandinelli, S. and
Chasman, D. I. and Grodstein, F. and Räikkönen, K. and
Lambert, J-C and Porteous, D. J. and Price, J. F. and
Sachdev, P. S. and Ferrucci, L. and Attia, J. R. and Rudan,
I. and Hayward, C. and Wright, A. F. and Wilson, J. F. and
Cichon, S. and Franke, L. and Schmidt, H. and Ding, J. and
de Craen, A. J. M. and Fornage, M. and Bennett, D. A. and
Deary, I. J. and Ikram, M. A. and Launer, L. J. and
Fitzpatrick, A. L. and Seshadri, S. and van Duijn, C. M. and
Mosley, T. H.},
collaboration = {Scotland, Generation},
title = {{GWAS} for executive function and processing speed suggests
involvement of the {CADM}2 gene},
journal = {Molecular psychiatry},
volume = {21},
issn = {1476-5578},
address = {London},
publisher = {Macmillan},
reportid = {FZJ-2015-03293},
pages = {189–197},
year = {2016},
abstract = {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.Molecular Psychiatry advance online publication, 14
April 2015; doi:10.1038/mp.2015.37.},
cin = {INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {571 - Connectivity and Activity (POF3-571)},
pid = {G:(DE-HGF)POF3-571},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25869804},
UT = {WOS:000370817800005},
doi = {10.1038/mp.2015.37},
url = {https://juser.fz-juelich.de/record/200955},
}