title: Imaging-genetics in dyslexia: connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments.
abstract: Dyslexia is a common pediatric disorder that affects 5-17% of schoolchildren in the United States. It is marked by unexpected difficulties in fluent reading despite adequate intelligence, opportunity, and instruction. Classically, neuropsychologists have studied dyslexia using a variety of neurocognitive batteries to gain insight into the specific deficits and impairments in affected children. Since dyslexia is a complex genetic trait with high heritability, analyses conditioned on performance on these neurocognitive batteries have been used to try to identify associated genes. This has led to some successes in identifying contributing genes, although much of the heritability remains unexplained. Additionally, the lack of relevant human brain tissue for analysis and the challenges of modeling a uniquely human trait in animals are barriers to advancing our knowledge of the underlying pathophysiology. In vivo imaging technologies, however, present new opportunities to examine dyslexia and reading skills in a clearly relevant context in human subjects. Recent investigations have started to integrate these imaging data with genetic data in attempts to gain a more complete and complex understanding of reading processes. In addition to bridging the gap from genetic risk variant to a discernible neuroimaging phenotype and ultimately to the clinical impairments in reading performance, the use of neuroimaging phenotypes will reveal novel risk genes and variants. In this article, we briefly discuss the genetic and imaging investigations and take an in-depth look at the recent imaging-genetics investigations of dyslexia.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Eicher
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
mesh_terms: D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D004410:Dyslexia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D059906:Neuroimaging
keywords: Dyslexia; Genetics; Imaging-genetics; Neuroimaging
references.citation: Mol Endocrinol. 2012 Apr;26(4):619-29
references.pmid: 22383464
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3117-22
references.pmid: 18287060
references.citation: Genes Brain Behav. 2007 Oct;6(7):640-6
references.pmid: 17309662
references.citation: Arch Neurol. 1997 May;54(5):562-73
references.pmid: 9152113
references.citation: Am J Hum Genet. 2008 Jan;82(1):165-73
references.pmid: 18179895
references.citation: J Mol Neurosci. 2005;27(3):311-4
references.pmid: 16280601
references.citation: Brain. 2005 Oct;128(Pt 10):2453-61
references.pmid: 15975942
references.citation: J Child Psychol Psychiatry. 2000 Jul;41(5):637-44
references.pmid: 10946755
references.citation: Ment Retard Dev Disabil Res Rev. 2007;13(1):96-105
references.pmid: 17326114
references.citation: Biol Psychiatry. 2011 Aug 1;70(3):237-45
references.pmid: 21457949
references.citation: N Engl J Med. 2008 Nov 27;359(22):2337-45
references.pmid: 18987363
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12695-700
references.pmid: 9770548
references.citation: Hum Mol Genet. 2007 Mar 15;16(6):667-77
references.pmid: 17309879
references.citation: Brain. 2002 Mar;125(Pt 3):465-78
references.pmid: 11872605
references.citation: Genes Brain Behav. 2010 Jun 1;9(4):390-401
references.pmid: 20132318
references.citation: Genes Brain Behav. 2011 Mar;10(2):158-65
references.pmid: 20846247
references.citation: J Cell Biol. 2003 Sep 15;162(6):1149-60
references.pmid: 12963709
references.citation: Neuropsychologia. 2005;43(3):324-31
references.pmid: 15707610
references.citation: Lancet. 2012 May 26;379(9830):1997-2007
references.pmid: 22513218
references.citation: Biol Psychiatry. 2013 Mar 15;73(6):583-90
references.pmid: 23036959
references.citation: Eur J Hum Genet. 2012 Feb;20(2):224-9
references.pmid: 21897444
references.citation: Mol Neurobiol. 2013 Feb;47(1):435-42
references.pmid: 23229871
references.citation: Mol Psychiatry. 2008 Mar;13(3):261-6
references.pmid: 17646849
references.citation: Behav Genet. 2011 Jan;41(1):77-89
references.pmid: 21207242
references.citation: PLoS One. 2012;7(12):e52166
references.pmid: 23300604
references.citation: Am J Hum Genet. 2002 May;70(5):1287-98
references.pmid: 11951179
references.citation: Neuroimage. 2010 Nov 15;53(3):1030-42
references.pmid: 20176116
references.citation: Neuroscience. 2008 Mar 27;152(3):723-33
references.pmid: 18313856
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17053-8
references.pmid: 16278297
references.citation: Am J Hum Genet. 2013 Jul 11;93(1):19-28
references.pmid: 23746548
references.citation: Genomics. 2003 Jul;82(1):1-9
references.pmid: 12809671
references.citation: J Neurodev Disord. 2011 Mar;3(1):39-49
references.pmid: 21484596
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4234-9
references.pmid: 17360506
references.citation: J Neurosci. 2013 Feb 20;33(8):3500-4
references.pmid: 23426677
references.citation: Am J Hum Genet. 2008 Jan;82(1):160-4
references.pmid: 18179894
references.citation: Brain Imaging Behav. 2008 Mar;2(1):21-26
references.pmid: 19096528
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):447-462
references.pmid: 19588467
references.citation: Neuroscience. 2011 Jan 13;172:535-46
references.pmid: 21070838
references.citation: Behav Genet. 2012 Jul;42(4):509-27
references.pmid: 22426781
references.citation: Neuron. 2012 Feb 9;73(3):537-52
references.pmid: 22325205
references.citation: J Neurosci. 2012 Jan 18;32(3):817-25
references.pmid: 22262880
references.citation: Brain Lang. 2012 Mar;120(3):360-71
references.pmid: 22281240
references.citation: Science. 2001 Mar 16;291(5511):2165-7
references.pmid: 11251124
references.citation: Brain. 2002 Mar;125(Pt 3):452-64
references.pmid: 11872604
references.citation: Neuropsychologia. 2012 Jun;50(7):1353-61
references.pmid: 22401987
references.citation: J Med Genet. 2003 May;40(5):340-5
references.pmid: 12746395
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9643-8
references.pmid: 15983371
references.citation: Eur J Hum Genet. 2007 Jun;15(6):711-3
references.pmid: 17392702
references.citation: Mol Psychiatry. 2004 Dec;9(12):1111-21
references.pmid: 15249932
references.citation: Neuron. 2010 Oct 21;68(2):309-20
references.pmid: 20955937
references.citation: Neurology. 2004 Aug 24;63(4):742-5
references.pmid: 15326259
references.citation: Brain Res Bull. 2007 Mar 15;71(5):508-14
references.pmid: 17259020
references.citation: Am J Hum Genet. 2004 Dec;75(6):1046-58
references.pmid: 15514892
references.citation: J Neurosci. 2013 Jan 2;33(1):244-58
references.pmid: 23283338
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2156-61
references.pmid: 22308323
references.citation: Neuroimage. 2005 May 1;25(4):1266-71
references.pmid: 15850744
references.citation: Behav Genet. 2011 Jan;41(1):50-7
references.pmid: 20949370
references.citation: Psychiatr Genet. 2008 Dec;18(6):310-2
references.pmid: 19018237
references.citation: Int J Dev Neurosci. 2013 Apr;31(2):116-22
references.pmid: 23220223
references.citation: J Med Genet. 1999 Sep;36(9):664-9
references.pmid: 10507721
references.citation: Brain Lang. 2012 Apr;121(1):1-11
references.pmid: 22377262
references.citation: Hum Genet. 2004 Jul;115(2):128-38
references.pmid: 15138886
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):556-60
references.pmid: 17450541
references.citation: Genesis. 2007 Jul;45(7):440-6
references.pmid: 17619227
references.citation: Mol Biol Evol. 2008 Jul;25(7):1257-9
references.pmid: 18413354
references.citation: PLoS Genet. 2011 Jul;7(7):e1002145
references.pmid: 21765815
references.citation: Biol Psychiatry. 2012 Oct 15;72(8):671-6
references.pmid: 22683091
references.citation: Hum Mol Genet. 2006 May 15;15(10):1659-66
references.pmid: 16600991
references.citation: Science. 1994 Oct 14;266(5183):276-9
references.pmid: 7939663
references.citation: Nature. 2002 Aug 22;418(6900):869-72
references.pmid: 12192408
references.citation: Genes Brain Behav. 2010 Oct;9(7):732-40
references.pmid: 20528955
references.citation: Mol Biol Evol. 2009 Oct;26(10):2181-4
references.pmid: 19608635
references.citation: Brain. 1996 Feb;119 ( Pt 1):143-57
references.pmid: 8624677
references.citation: J Neural Transm (Vienna). 2010 Jul;117(7):827-30
references.pmid: 20532925
references.citation: Schizophr Res. 2011 Jul;129(2-3):141-8
references.pmid: 21507613
references.citation: J Learn Disabil. 2000 Jul-Aug;33(4):334-58
references.pmid: 15493096
references.citation: Am J Hum Genet. 2005 Jun;76(6):1074-80
references.pmid: 15877281
references.citation: Cell. 2009 May 29;137(5):961-71
references.pmid: 19490899
references.citation: Am J Hum Genet. 1999 Jan;64(1):157-64
references.pmid: 9915954
references.citation: Eur J Hum Genet. 2010 Jun;18(6):668-73
references.pmid: 20068590
references.citation: Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8939-44
references.pmid: 9671783
references.citation: Nat Neurosci. 2003 Nov;6(11):1230-7
references.pmid: 14555953
references.citation: Neuroscience. 2011 Feb 23;175:75-84
references.pmid: 21111790
references.citation: Cereb Cortex. 2007 Nov;17(11):2562-72
references.pmid: 17218481
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17849-54
references.pmid: 17978184
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):146-56
references.pmid: 23341075
references.citation: N Engl J Med. 1998 Jan 29;338(5):307-12
references.pmid: 9445412
references.citation: Am J Psychiatry. 2008 Dec;165(12):1576-84
references.pmid: 18829873
references.citation: Twin Res Hum Genet. 2007 Jun;10(3):434-9
references.pmid: 17564501
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2011 Dec;156B(8):941-8
references.pmid: 21987501
references.citation: Nat Genet. 1998 Feb;18(2):168-70
references.pmid: 9462748
references.citation: Neuroscience. 2006 Dec 1;143(2):515-22
references.pmid: 16989952
references.citation: J Neurosci. 2004 Oct 20;24(42):9250-60
references.pmid: 15496660
references.citation: Hum Mol Genet. 2006 Nov 1;15(21):3154-67
references.pmid: 16984964
references.citation: Curr Biol. 2008 Mar 11;18(5):354-62
references.pmid: 18328704
references.citation: Cereb Cortex. 2010 Apr;20(4):884-97
references.pmid: 19679544
references.citation: Hum Genet. 2005 Oct;118(1):87-90
references.pmid: 16133186
references.citation: Brain. 1999 Oct;122 ( Pt 10):1901-17
references.pmid: 10506092
references.citation: Curr Opin Neurobiol. 2011 Jun;21(3):415-24
references.pmid: 21592779
references.citation: J Neurogenet. 2008;22(4):295-313
references.pmid: 19085271
references.citation: Genes Brain Behav. 2011 Mar;10(2):244-52
references.pmid: 20977651
references.citation: Am J Hum Genet. 2007 Dec;81(6):1232-50
references.pmid: 17999362
references.citation: Ann N Y Acad Sci. 2008 Dec;1145:237-59
references.pmid: 19076401
references.citation: PLoS Genet. 2005 Oct;1(4):e50
references.pmid: 16254601
references.citation: PLoS One. 2013 May 15;8(5):e63762
references.pmid: 23691092
references.citation: Am J Hum Genet. 2005 Apr;76(4):581-91
references.pmid: 15717286
references.citation: Brain Imaging Behav. 2013 Mar;7(1):15-27
references.pmid: 22669497
references.citation: Arch Neurol. 1992 May;49(5):527-34
references.pmid: 1580816
references.citation: Genes Brain Behav. 2011 Nov;10(8):868-75
references.pmid: 21883923
references.citation: Neuron. 2000 Feb;25(2):493-500
references.pmid: 10719902
references.citation: Behav Genet. 2011 Jan;41(1):90-104
references.pmid: 21165691
references.citation: Neuroimage. 2012 Oct 15;63(1):148-56
references.pmid: 22750057
references.citation: Hum Brain Mapp. 2003 Mar;18(3):194-200
references.pmid: 12599277
references.citation: Mol Psychiatry. 2006 Dec;11(12):1085-91, 1061
references.pmid: 17033633
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2012 Dec;159B(8):970-6
references.pmid: 23065966
references.citation: Int J Dev Neurosci. 2012 Jun;30(4):293-302
references.pmid: 22326444
references.citation: Cortex. 2005 Jun;41(3):354-63
references.pmid: 15871600
references.citation: PLoS One. 2012;7(11):e50321
references.pmid: 23209710
references.citation: Neuropsychologia. 2006;44(11):2178-88
references.pmid: 16524602
references.citation: Nature. 1987 Oct 8-14;329(6139):537-9
references.pmid: 3657975
references.citation: Behav Genet. 2011 Jan;41(1):58-66
references.pmid: 21042874
references.citation: Am J Hum Genet. 2008 Jan;82(1):150-9
references.pmid: 18179893
references.citation: Curr Opin Neurobiol. 2013 Feb;23(1):43-51
references.pmid: 23228431
references.citation: Eur J Hum Genet. 2005 Apr;13(4):491-9
references.pmid: 15702132
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2636-41
references.pmid: 9482939
references.citation: Cognition. 2006 Sep;101(2):385-413
references.pmid: 16844106
references.citation: Curr Biol. 2007 Nov 6;17(21):1908-12
references.pmid: 17949978
references.citation: Brain. 2012 Mar;135(Pt 3):935-48
references.pmid: 22327793
references.citation: PLoS One. 2011;6(6):e20580
references.pmid: 21698230
references.citation: Psychiatr Genet. 2012 Feb;22(1):25-30
references.pmid: 21881542
references.citation: Ann Dyslexia. 2009 Jun;59(1):1-11
references.pmid: 19238550
references.citation: Mol Psychiatry. 2010 Dec;15(12):1190-6
references.pmid: 19901951
references.citation: PLoS Genet. 2009 Mar;5(3):e1000436
references.pmid: 19325871
references.citation: J Commun Disord. 2008 Sep-Oct;41(5):409-20
references.pmid: 18466916
references.citation: Cell. 2011 Sep 30;147(1):235-46
references.pmid: 21962519
references.citation: Psychiatr Genet. 2009 Apr;19(2):59-63
references.pmid: 19240663
references.citation: Biol Psychiatry. 2007 Oct 1;62(7):811-7
references.pmid: 17597587
references.citation: Annu Rev Psychol. 2009;60:283-306
references.pmid: 18652545
references.citation: Am J Hum Genet. 2006 Jan;78(1):52-62
references.pmid: 16385449
references.citation: Hum Genet. 2004 Apr;114(5):510-6
references.pmid: 15007729
references.citation: Genes Brain Behav. 2011 Jun;10(4):451-6
references.pmid: 21310003
references.citation: J Med Genet. 2000 Oct;37(10):771-5
references.pmid: 11015455
references.citation: Neuron. 1999 Dec;24(4):1037-47
references.pmid: 10624965
references.citation: Neurology. 2001 Mar 27;56(6):781-3
references.pmid: 11274316
references.citation: Nature. 2001 Oct 4;413(6855):519-23
references.pmid: 11586359
references.citation: Sci Transl Med. 2010 Nov 3;2(56):56ra80
references.pmid: 21048216
references.citation: Dev Psychopathol. 2008 Fall;20(4):1329-49
references.pmid: 18838044