You are here
GWAS for executive function and processing speed suggests involvement of the CADM2 gene.
Friday,2015-08-28 10:16 America/Los_Angeles — zdrager
| Title | GWAS for executive function and processing speed suggests involvement of the CADM2 gene. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, deJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA, Palotie, A, Hsieh, Y-C, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, Chasman, DI, Grodstein, F, Räikkönen, K, Lambert, J-C, Porteous, DJ, Price, JF, Sachdev, PS, Ferrucci, L, Attia, JR, Rudan, I, Hayward, C, Wright, AF, Wilson, JF, Cichon, S, Franke, L, Schmidt, H, Ding, J, de Craen, AJM, Fornage, M, Bennett, DA, Deary, IJ, Ikram, MA, Launer, LJ, Fitzpatrick, AL, Seshadri, S, van Duijn, CM, Mosley, TH |
| Corporate/Institutional Authors | Generation Scotland |
| Journal | Mol Psychiatry |
| Volume | 21 |
| Issue | 2 |
| Pagination | 189-97 |
| Date Published | 2016 Feb |
| ISSN | 1476-5578 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/mp.2015.37 |
| Alternate Journal | Mol. Psychiatry |
| PubMed ID | 25869804 |
| PubMed Central ID | PMC4722802 |
| Grant List | 1R01AG032098-01A1 / AG / NIA NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States 263 MD821336 / MD / NIMHD NIH HHS / United States 263 MD9164 13 / MD / NIMHD NIH HHS / United States 263 MD9164 13 / MD / NIMHD NIH HHS / United States 5UO1CA098233 / CA / NCI NIH HHS / United States AG008122 / AG / NIA NIH HHS / United States AG033193 / 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 CZD/16/6 / / Chief Scientist Office / United Kingdom CZD/16/6/4 / / 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 HHSN268200782096C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268200900020C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States HHSN268201100006C / / PHS HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States HHSN268201100010C / / PHS HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States HHSN268201100012C / / PHS HHS / United States HHSN268201200036C / HL / NHLBI NIH 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 K08 AG034290 / AG / NIA NIH HHS / United States K08AG34290 / AG / NIA NIH HHS / United States K25 AG041906 / 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 AG012100 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01 AG821336 / AG / NIA NIH HHS / United States N01 AG916413 / AG / NIA NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N01[AG] 821336 / AG / NIA NIH HHS / United States N01[AG]916413 / AG / NIA NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States NHLBIU01HL080295 / / PHS HHS / United States NS041558 / NS / NINDS NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States P01 CA055075 / CA / NCI NIH HHS / United States P01 CA087969 / CA / NCI NIH HHS / United States P01 DK070756 / DK / NIDDK 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 P50 AG005133 / AG / NIA NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States R01 AG016495 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States R01 AG030146 / AG / NIA NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 CA047988 / CA / NCI NIH HHS / United States R01 CA049449 / CA / NCI NIH HHS / United States R01 CA050385 / CA / NCI NIH HHS / United States R01 CA065725 / CA / NCI NIH HHS / United States R01 CA067262 / CA / NCI NIH HHS / United States R01 CA134958 / CA / NCI NIH HHS / United States R01 DK058845 / DK / NIDDK NIH HHS / United States R01 EY009611 / EY / NEI NIH HHS / United States R01 EY015473 / EY / NEI NIH HHS / United States R01 HL034594 / HL / NHLBI NIH HHS / United States R01 HL035464 / HL / NHLBI NIH HHS / United States R01 HL043851 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL070825 / HL / NHLBI NIH HHS / United States R01 HL071917 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL080467 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL087660 / HL / NHLBI NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States R01 NS041558 / NS / NINDS NIH HHS / United States R01AG023629 / AG / NIA NIH HHS / United States R01AG027058 / AG / NIA NIH HHS / United States R01AG15819 / AG / NIA NIH HHS / United States R01AG15928 / AG / NIA NIH HHS / United States R01AG17917 / AG / NIA NIH HHS / United States R01AG20098 / AG / NIA NIH HHS / United States R01AG30146 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States R01HL103612 / HL / NHLBI NIH HHS / United States R01HL105756 / HL / NHLBI NIH HHS / United States R01HL120393 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States R01HL70825 / HL / NHLBI NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01 CA067262 / CA / NCI NIH HHS / United States U01 CA098233 / CA / NCI NIH HHS / United States U01 HG004399 / HG / NHGRI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01 HG004728 / HG / NHGRI NIH HHS / United States U01 HL054457 / HL / NHLBI NIH HHS / United States U01 HL054463 / HL / NHLBI NIH HHS / United States U01 HL054464 / HL / NHLBI NIH HHS / United States U01 HL054481 / HL / NHLBI NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U01HG004399 / HG / NHGRI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States WT089062 / / Wellcome Trust / United Kingdom / / Biotechnology and Biological Sciences Research Council / United Kingdom / / British Heart Foundation / United Kingdom / / Intramural NIH HHS / United States / / Medical Research Council / United Kingdom |