Variation in GRIN2B contributes to weak performance in verbal short‐term memory in children with dyslexia

A multi‐marker haplotype within GRIN2B, a gene coding for a subunit of the ionotropic glutamate receptor, has recently been found to be associated with variation in human memory performance [de Quervain and Papassotiropoulos, 2006 ]. The gene locus is located within a region that has been linked to a phonological memory phenotype in a recent genome scan in families with dyslexia [Brkanac et al., 2008 ]. These findings may indicate the involvement of GRIN2B in memory‐related aspects of human cognition. Memory performance is one of the cognitive functions observed to be disordered in dyslexia patients. We therefore investigated whether genetic variation in GRIN2B contributes to specific quantitative measures in a German dyslexia sample by genotyping 66 SNPs in its entire genomic region. We found supportive evidence that markers in intron 3 are associated with short‐term memory in dyslexia, and were able to demonstrate that this effect is even stronger when only maternal transmission is considered. These results suggest that variation within GRIN2B may contribute to the genetic background of specific cognitive processes which are correlates of the dyslexia phenotype. © 2009 Wiley‐Liss, Inc.

[1]  S. Pickering,et al.  Working memory in dyslexia , 2012 .

[2]  S. Cichon,et al.  Supporting evidence for LRRTM1 imprinting effects in schizophrenia , 2009, Molecular Psychiatry.

[3]  Richard Wade-Martins,et al.  A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene , 2009, PLoS genetics.

[4]  Todd Richards,et al.  A Multidisciplinary Approach to Understanding Developmental Dyslexia Within Working-Memory Architecture: Genotypes, Phenotypes, Brain, and Instruction , 2008, Developmental neuropsychology.

[5]  E. Wijsman,et al.  Genome Scan of a Nonword Repetition Phenotype in Families with Dyslexia: Evidence for Multiple Loci , 2008, Behavior genetics.

[6]  M. Nöthen,et al.  Genetics and Neuroscience in Dyslexia: Perspectives for Education and Remediation. , 2007 .

[7]  A. Monaco,et al.  The genetic lexicon of dyslexia. , 2007, Annual review of genomics and human genetics.

[8]  D. Geschwind,et al.  LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia , 2007, Molecular Psychiatry.

[9]  R Tannock,et al.  Association of the glutamate receptor subunit gene GRIN2B with attention‐deficit/hyperactivity disorder , 2007, Genes, brain, and behavior.

[10]  Patrick F. Sullivan,et al.  Spurious Genetic Associations , 2007, Biological Psychiatry.

[11]  Heikki Lyytinen,et al.  A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia. , 2007, Human molecular genetics.

[12]  N. Laurin,et al.  No preferential transmission of paternal alleles at risk genes in attention-deficit hyperactivity disorder , 2007, Molecular Psychiatry.

[13]  A Ziegler,et al.  Interrelationship and Familiality of Dyslexia Related Quantitative Measures , 2007, Annals of human genetics.

[14]  M. Nöthen,et al.  Genetics of dyslexia: the evolving landscape , 2007, Journal of Medical Genetics.

[15]  M C O'Donovan,et al.  Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia , 2006, Molecular Psychiatry.

[16]  S. Gathercole,et al.  Working Memory and Neurodevelopmental Disorders , 2006 .

[17]  F. Ramus,et al.  From genes to behavior in developmental dyslexia , 2006, Nature Neuroscience.

[18]  B. Pennington.  From single to multiple deficit models of developmental disorders , 2006, Cognition.

[19]  B. Pennington,et al.  Processing Speed Deficits in Attention Deficit/Hyperactivity Disorder and Reading Disability , 2006, Journal of abnormal child psychology.

[20]  C. Francks,et al.  Genes, cognition and dyslexia: learning to read the genome , 2006, Trends in Cognitive Sciences.

[21]  Andreas Papassotiropoulos,et al.  Identification of a genetic cluster influencing memory performance and hippocampal activity in humans. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Gill,et al.  Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. , 2005, American journal of human genetics.

[23]  P. Skudlarski,et al.  DCDC2 is associated with reading disability and modulates neuronal development in the brain. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Juha Kere,et al.  The Axon Guidance Receptor Gene ROBO1 Is a Candidate Gene for Developmental Dyslexia , 2005, PLoS genetics.

[25]  R. Plomin,et al.  Generalist genes and learning disabilities. , 2005, Psychological bulletin.

[26]  Bertram Müller-Myhsok,et al.  Developmental Dyslexia – Recurrence Risk Estimates from a German Bi-Center Study Using the Single Proband Sib Pair Design , 2005, Human Heredity.

[27]  Peter Holmans,et al.  Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. , 2005, American journal of human genetics.

[28]  B. Pennington,et al.  Neuropsychological Analyses of Comorbidity Between Reading Disability and Attention Deficit Hyperactivity Disorder: In Search of the Common Deficit , 2005, Developmental neuropsychology.

[29]  C. Francks,et al.  A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States. , 2004, American journal of human genetics.

[30]  B. Pennington,et al.  Sensory processing, reading, IQ, and attention. , 2004, Journal of experimental child psychology.

[31]  B. Pennington,et al.  Refinement of the 6p21.3 quantitative trait locus influencing dyslexia: linkage and association analyses , 2004, Human Genetics.

[32]  S. Gathercole,et al.  A structural analysis of working memory and related cognitive skills in young children. , 2004, Journal of experimental child psychology.

[33]  A. Baddeley.  Working memory: looking back and looking forward , 2003, Nature Reviews Neuroscience.

[34]  Heikki Lyytinen,et al.  A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Richard K Olson,et al.  Dyslexia: nature and nurture. , 2002, Dyslexia.

[36]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[37]  D. Schaid,et al.  Incidence of reading disability in a population-based birth cohort, 1976-1982, Rochester, Minn. , 2001, Mayo Clinic proceedings.

[38]  R. Olson,et al.  Genetic and Environmental Influences on Orthographic and Phonological Skills in Children With Reading Disabilities , 2001, Developmental neuropsychology.

[39]  G. Schulte-Körne,et al.  Zur Diagnostik der Lese- Rechtschreibstörung , 2001 .

[40]  C. Francks,et al.  Investigation of Quantitative Measures Related to Reading Disability in a Large Sample of Sib-Pairs from the UK , 2001, Behavior genetics.

[41]  L. Wilkinson,et al.  Imprinted genes, cognition and behaviour , 2000, Trends in Cognitive Sciences.

[42]  Sue Palmer,et al.  Phonological recoding deficit in working memory of dyslexic teenagers , 2000 .

[43]  D. Francis,et al.  Persistence of dyslexia: the Connecticut Longitudinal Study at adolescence. , 1999, Pediatrics.

[44]  E. Taylor,et al.  Hyperactivity and reading disability: a longitudinal study of the nature of the association. , 1999, Journal of child psychology and psychiatry, and allied disciplines.

[45]  E. Shimizu,et al.  Genetic enhancement of learning and memory in mice , 1999, Nature.

[46]  S. Cichon,et al.  Evidence for linkage of spelling disability to chromosome 15. , 1998, American journal of human genetics.

[47]  A. Pizzuti,et al.  mRNA distribution in adult human brain of GRIN2B, a N-methyl-d-aspartate (NMDA) receptor subunit , 1997, Neuroscience Letters.

[48]  P. A. Jacobs,et al.  Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function , 1997, Nature.

[49]  H Remschmidt,et al.  Familial aggregation of spelling disability. , 1996, Journal of child psychology and psychiatry, and allied disciplines.

[50]  Masahiko Watanabe,et al.  Impairment of Suckling Response, Trigeminal Neuronal Pattern Formation, and Hippocampal LTD in NMDA Receptor ε2 Subunit Mutant Mice , 1996, Neuron.

[51]  B. Pennington,et al.  Hyperactivity and spelling disability: testing for shared genetic aetiology. , 1993, Journal of child psychology and psychiatry, and allied disciplines.

[52]  A Baddeley,et al.  A developmental deficit in short-term phonological memory: implications for language and reading. , 1993, Memory.

[53]  J. Fletcher,et al.  Prevalence of reading disability in boys and girls. Results of the Connecticut Longitudinal Study. , 1990, JAMA.

[54]  B. Cattanach,et al.  Differential activity of maternally and paternally derived chromosome regions in mice , 1985, Nature.

[55]  P. Bryant,et al.  Difficulties in auditory organisation as a possible cause of reading backwardness , 1978, Nature.

[56]  B HALLGREN,et al.  Specific Dyslexia (Congenital Word Blindness): A Clinical and Genetic Study , 1952, Acta psychiatrica et neurologica. Supplementum.

[57]  Franz Petermann,et al.  Hamburg-Wechsler-Intelligenztest für Kinder - IV , 2007 .

[58]  T. Banaschewski,et al.  Phonological short-term memory and central executive processing in attention-deficit/hyperactivity disorder with/without dyslexia – evidence of cognitive overlap , 2007, Journal of Neural Transmission.

[59]  Andreas Ziegler,et al.  Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia. , 2006, American journal of human genetics.

[60]  J. Fletcher,et al.  Specific reading disability (dyslexia): what have we learned in the past four decades? , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[61]  Lon R. Cardon,et al.  Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia , 2002, Nature Genetics.

[62]  H. Remschmidt,et al.  [Diagnosis of reading and spelling disorder]. , 2001, Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie.

[63]  B. Pennington,et al.  Reading disability and hyperactivity disorder: Evidence for a common genetic etiology , 1995 .