Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-24T21:23:31.713Z Has data issue: false hasContentIssue false
  • English
  • Français

Neurocognitive phenomics: examining the genetic basis of cognitive abilities

Published online by Cambridge University Press:  30 November 2012

G. Donohoe ,
I. J. Deary ,
D. C. Glahn ,
A. K. Malhotra  and
K. E. Burdick
G. Donohoe*
Affiliation:
Department of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland
I. J. Deary
Affiliation:
Department of Psychology, University of Edinburgh, Edinburgh, UK
D. C. Glahn
Affiliation:
Olin Neuropsychiatry Research Center, Institute of Living, and Department of Psychiatry, Yale University, New Haven, CT, USA
A. K. Malhotra
Affiliation:
The Zucker Hillside Hospital, Glen Oaks, NY, USA
K. E. Burdick
Affiliation:
Departments of Psychiatry and Neuroscience at Mount Sinai School of Medicine, New York, NY, USA
*
*Address for correspondence: G. Donohoe, DClinPsych, Ph.D., Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Republic of Ireland. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial: just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genome-wide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.

Keywords

CognitionendophenotypegeneticsGWASschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 43 , Issue 10 , October 2013 , pp. 2027 - 2036
Copyright
Copyright © Cambridge University Press 2012 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abrahams, BS, Geschwind, DH (2010). Connecting genes to brain in the autism spectrum disorders. Archives of Neurology 67, 395–399.CrossRefGoogle ScholarPubMed
Bearden, CE, Freimer, NB (2006). Endophenotypes for psychiatric disorders: ready for primetime? Trends in Genetics 22, 306–313.CrossRefGoogle ScholarPubMed
Bellgrove, MA, Mattingley, JB (2008). Molecular genetics of attention. Annals of the New York Academy of Science 1129, 200–212.CrossRefGoogle ScholarPubMed
Bidwell, LC, McClernon, FJ, Kollins, SH (2011). Cognitive enhancers for the treatment of ADHD. Pharmacology, Biochemistry and Behavior 99, 262–274.CrossRefGoogle ScholarPubMed
Bidwell, LC, Willcutt, EG, Defries, JC, Pennington, BF (2007). Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biological Psychiatry 62, 991–998.CrossRefGoogle ScholarPubMed
Bilder, RM, Howe, A, Novak, N, Sabb, FW, Parker, DS (2011). The genetics of cognitive impairment in schizophrenia: a phenomic perspective. Trends in Cognitive Sciences 15, 428–435.CrossRefGoogle ScholarPubMed
Butcher, LM, Davis, OS, Craig, IW, Plomin, R (2008). Genome-wide quantitative trait locus association scan of general cognitive ability using pooled DNA and 500k single nucleotide polymorphism microarrays. Genes, Brain, and Behavior 7, 435–446.CrossRefGoogle ScholarPubMed
Cannon, TD (2005). The inheritance of intermediate phenotypes for schizophrenia. Current Opinion in Psychiatry 18, 135–140.CrossRefGoogle ScholarPubMed
Cardno, AG, Marchall, JE, Coid, B, MacDonald, AM, Ribchester, TR, Davies, NJ, Venturi, P, Jones, LA, Lewis, SW, Sham, PC, Gottesman, II, Farmer, AE, McGuffin, P, Reveley, AM, Murray, RM (1999). Heritability estimates for psychotic disorders. Archives of General Psychiatry 56, 162–168.CrossRefGoogle ScholarPubMed
Carroll, JB (1993). Human Cognitive Abilities: A Survey of Factor-Analytical Studies. Cambridge University Press: New York.CrossRefGoogle Scholar
Corvin, A, Donohoe, G, Hargreaves, A, Gallagher, L, Gill, M (2012). The cognitive genetics of neuropsychiatric disorders. Current Topics in Behavioral Neuroscience 12, 579–613.CrossRefGoogle ScholarPubMed
Davidson, M, Galderisi, S, Weiser, M, Werbeloff, N, Fleischhacker, WW, Keefe, RS, Boter, H, Keet, IP, Prelipceanu, D, Rybakowski, JK, Libiger, J, Hummer, M, Dollfus, S, López-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens, J, Lindefors, N, Riecher-Rössler, A, Kahn, RS (2009). Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). American Journal of Psychiatry 166, 675–682.CrossRefGoogle ScholarPubMed
Davies, G, Tenesa, A, Payton, A, Yang, J, Harris, SE, Liewald, D, Ke, X, Le Hellard, S, Christoforou, A, Luciano, M, McGhee, K, Lopez, L, Gow, AJ, Corley, J, Redmond, P, Fox, HC, Haggarty, P, Whalley, LJ, McNeill, G, Goddard, ME, Espeseth, T, Lundervold, AJ, Reinvang, I, Pickles, A, Steen, VM, Ollier, W, Porteous, DJ, Horan, M, Starr, JM, Pendleton, N, Visscher, PM, Deary, IJ (2011). Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16, 996–1005.CrossRefGoogle ScholarPubMed
Deary, IJ (2001 a). Human intelligence differences: a recent history. Trends in Cognitive Sciences 5, 127–130.CrossRefGoogle ScholarPubMed
Deary, IJ (2001 b). Human intelligence differences: towards a combined experimental–differential approach. Trends in Cognitive Sciences 5, 164–170.CrossRefGoogle ScholarPubMed
Deary, IJ (2001 c). Individual differences in cognition: British contributions over a century. British Journal of Psychology 92, 217–237.CrossRefGoogle ScholarPubMed
Deary, IJ, Johnson, W, Houlihan, LM (2009). Genetic foundations of human intelligence. Human Genetics 126, 215–232.CrossRefGoogle ScholarPubMed
Deary, IJ, Penke, L, Johnson, W (2010). The neuroscience of human intelligence differences. Nature Reviews Neuroscience 11, 201–211.CrossRefGoogle ScholarPubMed
Deary, IJ, Whalley, LJ, Lemmon, H, Crawford, JR, Starr, JM (2000). The stability of individual differences in mental ability from childhood to old age: follow-up of the 1932 Scottish Mental Survey. Intelligence 28, 49–55.CrossRefGoogle Scholar
Donohoe, G, Corvin, A, Robertson, I (2006). Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile. Cognitive Neuropsychiatry 11, 13–32.CrossRefGoogle ScholarPubMed
Donohoe, G, Goldberg, TE, Corvin, A (2009). Cognitive intermediate phenotypes in schizophrenia genetics. In The Genetics of Cognitive Neuroscience (ed. Goldberg, T. E. and Weinberger, D.), pp. 195–220. MIT Press: Boston.CrossRefGoogle Scholar
Donohoe, G, Robertson, IH (2003). Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review. Neurocase 9, 97–108.CrossRefGoogle ScholarPubMed
Donohoe, G, Walters, J, Morris, DW, Da Costa, A, Rose, E, Hargreaves, A, Maher, K, Hayes, E, Giegling, I, Hartmann, AM, Möller, HJ, Muglia, P, Moskvina, V, Owen, MJ, O'Donovan, MC, Gill, M, Corvin, A, Rujescu, D (2011). A neuropsychological investigation of the genome wide associated schizophrenia risk variant NRGN rs12807809. Schizophrenia Research 125, 304–306.CrossRefGoogle ScholarPubMed
Erlenmeyer-Kimling, L, Rock, D, Roberts, SA, Janal, M, Kestenbaum, C, Cornblatt, B, Hilldoff Adamo, U, Gottesman, II (2000). Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. American Journal of Psychiatry 157, 1416–1422.CrossRefGoogle ScholarPubMed
Fowler, T, Zammit, S, Owen, MJ, Rasmussen, F (2012). A population-based study of shared genetic variation between premorbid IQ and psychosis among male twin pairs and sibling pairs from Sweden. Psychological Medicine 69, 460–466.Google ScholarPubMed
Glahn, DC, Bearden, CE, Niendam, TA, Escamilla, MA (2004). The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder. Bipolar Disorders 6, 171–182.CrossRefGoogle ScholarPubMed
Glahn, DC, Curran, JE, Winkler, AM, Carless, MA, Kent, JW, Charlesworth, JC, Johnson, MP, Goring, HH, Cole, SA, Dyer, TD, Moses, EK, Olvera, RL, Kochunov, P, Duggirala, R, Fox, PT, Almasy, L, Blangero, J (2012). High dimensional endophenotype ranking in the search for major depression risk genes. Biological Psychiatry 71, 6–14.CrossRefGoogle ScholarPubMed
Goldberg, TE, Ragland, JD, Torrey, EF, Gold, JM, Bigelow, LB, Weinberger, DR (1990). Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Archives of General Psychiatry 47, 1066–1072.CrossRefGoogle ScholarPubMed
Goldberg, TE, Torrey, EF, Gold, JM, Bigelow, LB, Ragland, RD, Taylor, E, Weinberger, DR (1995). Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder. Schizophrenia Research 17, 77–84.CrossRefGoogle ScholarPubMed
Goldberg, TE, Weinberger, DR (2004). Genes and the parsing of cognitive processes. Trends in Cognitive Sciences 8, 325–335.CrossRefGoogle ScholarPubMed
Good, KP, Rabinowitz, J, Whitehorn, D, Harvey, PD, DeSmedt, G, Kopala, LC (2004). The relationship of neuropsychological test performance with the PANSS in antipsychotic naive, first-episode psychosis patients. Schizophrenia Research 68, 11–19.CrossRefGoogle ScholarPubMed
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Green, MF, Kern, RS, Heaton, RK (2004). Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophrenia Research 72, 41–51.CrossRefGoogle ScholarPubMed
Gur, RE, Calkins, ME, Gur, RC, Horan, WP, Nuechterlein, KH, Seidman, LJ, Stone, WS (2007). The Consortium on the Genetics of Schizophrenia: neurocognitive endophenotypes. Schizophrenia Bulletin 33, 49–68.CrossRefGoogle Scholar
Johnson, W, Bouchard, TJ, Krueger, RF, McGue, M, Gottesman, II (2004). Just one g: consistent results from three test batteries. Intelligence 32, 95–107.CrossRefGoogle Scholar
Johnson, W, te Nijenhuis, J, Bouchard, TJ (2008). Still just 1 g: consistent results from five test batteries. Intelligence 36, 81–95.CrossRefGoogle Scholar
Jung, RE, Haier, RJ (2007). The Parieto-Frontal Integration Theory (P-FIT) of intelligence: converging neuroimaging evidence. Behavioral and Brain Sciences 30, 135–187.CrossRefGoogle ScholarPubMed
Lanktree, MB, Guo, Y, Murtaza, M, Glessner, JT, Bailey, SD, Onland-Moret, NC, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, CP, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, JS, Shah, S, Taylor, K, Barnard, J, Peters, BJ, Maloney, CM, Lobmeyer, MT, Stanton, A, Zafarmand, MH, Romaine, SP, Mehta, A, van Iperen, EP, Gong, Y, Price, TS, Smith, EN, Kim, CE, Li, YR, Asselbergs, FW, Atwood, LD, Bailey, KM, Bhatt, D, Bauer, F, Behr, ER, Bhangale, T, Boer, JM, Boehm, BO, Bradfield, JP, Brown, M, Braund, PS, Burton, PR, Carty, C, Chandrupatla, HR, Chen, W, Connell, J, Dalgeorgou, C, Boer, A, Drenos, F, Elbers, CC, Fang, JC, Fox, CS, Frackelton, EC, Fuchs, B, Furlong, CE, Gibson, Q, Gieger, C, Goel, A, Grobbee, DE, Hastie, C, Howard, PJ, Huang, GH, Johnson, WC, Li, Q, Kleber, ME, Klein, BE, Klein, R, Kooperberg, C, Ky, B, Lacroix, A, Lanken, P, Lathrop, M, Li, M, Marshall, V, Melander, O, Mentch, FD, Meyer, NJ, Monda, KL, Montpetit, A, Murugesan, G, Nakayama, K, Nondahl, D, Onipinla, A, Rafelt, S, Newhouse, SJ, Otieno, FG, Patel, SR, Putt, ME, Rodriguez, S, Safa, RN, Sawyer, DB, Schreiner, PJ, Simpson, C, Sivapalaratnam, S, Srinivasan, SR, Suver, C, Swergold, G, Sweitzer, NK, Thomas, KA, Thorand, B, Timpson, NJ, Tischfield, S, Tobin, M, Tomaszewski, M, Verschuren, WM, Wallace, C, Winkelmann, B, Zhang, H, Zheng, D, Zhang, L, Zmuda, JM, Clarke, R, Balmforth, AJ, Danesh, J, Day, IN, Schork, NJ, de Bakker, PI, Delles, C, Duggan, D, Hingorani, AD, Hirschhorn, JN, Hofker, MH, Humphries, SE, Kivimaki, M, Lawlor, DA, Kottke-Marchant, K, Mega, JL, Mitchell, BD, Morrow, DA, Palmen, J, Redline, S, Shields, DC, Shuldiner, AR, Sleiman, PM, Smith, GD, Farrall, M, Jamshidi, Y, Christiani, DC, Casas, JP, Hall, AS, Doevendans, PA, Christie, JD, Berenson, GS, Murray, SS, Illig, T, Dorn, GW 2nd, Cappola, TP, Boerwinkle, E, Sever, P, Rader, DJ, Reilly, MP, Caulfield, M, Talmud, PJ, Topol, E, Engert, JC, Wang, K, Dominiczak, A, Hamsten, A, Curtis, SP, Silverstein, RL, Lange, LA, Sabatine, MS, Trip, M, Saleheen, D, Peden, JF, Cruickshanks, KJ, Marz, W, O'Connell, JR, Klungel, OH, Wijmenga, C, Maitland-van der Zee, AH, Schadt, EE, Johnson, JA, Jarvik, GP, Papanicolaou, GJ, Grant, SF, Munroe, PB, North, KE, Samani, NJ, Koenig, W, Gaunt, TR, Anand, SS, van der Schouw, YT, Soranzo, N, Fitzgerald, GA, Reiner, A, Hegele, RA, Hakonarson, H, Keating, BJ (2011). Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height. American Journal of Human Genetics 88, 6–18.CrossRefGoogle ScholarPubMed
Lipkovich, IA, Deberdt, W, Csernansky, JG, Sabbe, B, Keefe, RS, Kollack-Walker, S (2009). Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy. BMC Psychiatry 9, 44.CrossRefGoogle ScholarPubMed
Luciano, M, Hansell, NK, Lahti, J, Davies, G, Medland, SE, Räikkönen, K, Tenesa, A, Widen, E, McGhee, KA, Palotie, A, Liewald, D, Porteous, DJ, Starr, JM, Montgomery, GW, Martin, NG, Eriksson, JG, Wright, MJ, Deary, IJ (2011). Whole genome association scan for genetic polymorphisms influencing information processing speed. Biological Psychology 86, 193–202.CrossRefGoogle ScholarPubMed
Luciano, M, Wright, MJ, Geffen, GM, Geffen, LB, Smith, GA, Martin, NG (2004). A genetic investigation of the covariation among inspection time, choice reaction time, and IQ subtest scores. Behavior Genetics 34, 41–50.CrossRefGoogle ScholarPubMed
MacLullich, AMJ, Ferguson, KJ, Deary, IJ, Seckl, JR, Starr, JM, Wardlaw, JM (2002). Intracranial capacity and brain volumes are associated with cognition in healthy elderly men. Neurology 59, 169–174.CrossRefGoogle ScholarPubMed
MacQueen, G, Frodl, T (2011). The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Molecular Psychiatry 16, 252–264.CrossRefGoogle ScholarPubMed
Manolio, TA (2010). Genomewide association studies and assessment of the risk of disease. New England Journal of Medicine 363, 166–176.CrossRefGoogle ScholarPubMed
McGuffin, P, Rijsdijk, F, Andrew, M, Sham, P, Katz, R, Cardno, A (2003). The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry 60, 497–502.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A, Weinberger, DR (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews Neuroscience 7, 818–827.CrossRefGoogle ScholarPubMed
Need, AC, Attix, DK, McEvoy, JM, Cirulli, ET, Linney, KL, Hunt, P, Ge, D, Heinzen, EL, Maia, JM, Shianna, KV, Weale, ME, Cherkas, LF, Clement, G, Spector, TD, Gibson, G, Goldstein, DB (2009). A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Human Molecular Genetics 18, 4650–4661.CrossRefGoogle ScholarPubMed
Papassotiropoulos, A, Stephan, DA, Huentelman, MJ, Hoerndli, FJ, Craig, DW, Pearson, JV, Huynh, K, Brunner, F, Corneveaux, J, Osborne, D, Wollmer, MA, Aerni, A, Coluccia, D, Hanggi, J, Mondadori, CRA, Buchman, A, Reiman, EM, Caselli, RJ, Henke, K, de Quervain, DJF (2006). Common Kibra alleles are associated with human memory performance. Science 314, 475–478.CrossRefGoogle ScholarPubMed
Payton, A (2009). The impact of genetic research on our understanding of normal cognitive ageing: 1995 to 2009. Neuropsychology Review 19, 451–477.CrossRefGoogle ScholarPubMed
Rijsdijk, FA, Vernon, PA, Boomsma, DI (2002). Application of hierarchical genetic models to Raven and WAIS subtests: a Dutch twin study. Behavior Genetics 32, 199–210.CrossRefGoogle ScholarPubMed
Rose, EJ, Donohoe, G (2012). Brain vs behavior: an effect size comparison of neuroimaging and cognitive studies of genetic risk for schizophrenia. Schizophrenia Bulletin. Published online 12 April 2012. doi:10.1093/schbul/sbs056.Google ScholarPubMed
Salthouse, TA (2004). Localising age-related individual differences in a hierarchical structure. Intelligence 32, 541–561.CrossRefGoogle Scholar
Seidman, LJ, Giuliano, AJ, Meyer, EC, Addington, J, Cadenhead, KS, Cannon, TD, McGlashan, TH, Perkins, DO, Tsuang, MT, Walker, EF, Woods, SW, Bearden, CE, Christensen, BK, Hawkins, K, Heaton, R, Keefe, RS, Heinssen, R, Cornblatt, BA; North American Prodrome Longitudinal Study (NAPLS) Group (2010). Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Archives of General Psychiatry 67, 578–588.CrossRefGoogle ScholarPubMed
Seshadri, S, DeStefano, AL, Au, R, Massaro, JM, Beiser, AS, Kelly-Hayes, M, Kase, CS, D'Agostino, RB Sr, Decarli, C, Atwood, LD, Wolf, PA (2007). Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study. BMC Medical Genetics 8 (Suppl. 1), S15.CrossRefGoogle Scholar
Spearman, C (1904). ‘“General intelligence,’ objectively determined and measured”. American Journal of Psychology 15, 201–293.CrossRefGoogle Scholar
Toulopoulou, T, Picchioni, M, Rijsdijk, F, Hua-Hall, M, Ettinger, U, Sham, P, Murray, R (2007). Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples. Archives of General Psychiatry 64, 1348–1355.CrossRefGoogle ScholarPubMed
Vernon, PE (1940). The Measurement of Abilities. University of London Press: London.Google Scholar
Walters, JT, Owen, MJ (2007). Endophenotypes in psychiatric genetics. Molecular Psychiatry 12, 886–890.CrossRefGoogle ScholarPubMed
Wykes, T, Huddy, V, Cellard, C, McGurk, SR, Czobor, P (2011). A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. American Journal of Psychiatry 168, 472–485.CrossRefGoogle ScholarPubMed
Zhang, Q, Shen, Q, Xu, Z, Chen, M, Cheng, L, Zhai, J, Gu, H, Bao, X, Chen, X, Wang, K, Deng, X, Ji, F, Liu, C, Li, J, Dong, Q, Chen, C (2012). The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder. Neuropsychopharmacology 37, 677–684.CrossRefGoogle ScholarPubMed