Gene discovery through imaging genetics: Identification of two novel genes associated with schizophrenia

Molecular Psychiatry

Volumn 14, Issue 4, 2009, Pages 416-428

  Potkin, S G ^a   Turner, J A ^a   Fallon, J A ^a   Lakatos, A ^a   Keator, D B ^a   Guffanti, G ^b   Macciardi, F ^b   Lauriello, John ^a,c   Bastillo, Juan ^a,c   O'Leary, Daniel ^a,d   Lim, Kelvin ^a,e   McCarthy, Gregory ^a,f   Ford, Judith ^a,f   Toga, Arthur ^a,g   Cannon, Tyrone ^a,g   Gollub, Randy ^a,h   Belger, Aysenil ^a,i   Nguyen, Dana ^a,j   Highum, Diane ^a,j  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF NEW MEXICO   (United States)

^d UNIVERSITY OF IOWA   (United States)

^e UNIVERSITY OF MINNESOTA   (United States)

^f YALE UNIVERSITY   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h HARVARD UNIVERSITY   (United States)

ⁱ UNIVERSITY OF NORTH CAROLINA   (United States)

^j UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

Case control study; Cognition; fMRI; GWAS; Prefrontal cortex; Quantitative trait loci

Indexed keywords

ARGININE SERINE RICH COILED COIL 1; ATYPICAL ANTIPSYCHOTIC AGENT; GENE PRODUCT; NEUROLEPTIC AGENT; RHO GTPASE ACTIVATING PROTEIN 18; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; BRAIN DEVELOPMENT; CONTROLLED STUDY; FALSE POSITIVE RESULT; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE; GENE IDENTIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC CODE; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; IMAGE ENHANCEMENT; MAJOR CLINICAL STUDY; MEMORY; NEUROIMAGING; PHENOTYPE; PREFRONTAL CORTEX; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM; TASK PERFORMANCE;

ADOLESCENT; ADULT; AGED; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENETIC SCREENING; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; GTPASE-ACTIVATING PROTEINS; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NUCLEAR PROTEINS; OXYGEN; POLYMORPHISM, SINGLE NUCLEOTIDE; PREFRONTAL CORTEX; SCHIZOPHRENIA; TUMOR SUPPRESSOR PROTEINS; YOUNG ADULT;

EID: 62849093626     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2008.127     Document Type: Article

References (72)

1. McQueen MB, Devlin B, Faraone SV, Nimgaonkar VL, Sklar P, Smoller JW et al. Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q. Am J Hum Genet 2005; 77: 582-595.
2. Vicente AM, Macciardi F, Verga M, Bassett AS, Honer WG, Bean G et al. NCAM and schizophrenia: genetic studies. Mol Psychiatry 1997; 2: 65-69.
3. Kwasnicka-Crawford DA, Roberts W, Scherer SW. Characterization of an Autism-Associated Segmental Maternal Heterodisomy of the Chromosome 15q11-13 Region. J Autism Dev Disord 2006; 37: 694-702.
4. Stein CM, Millard C, Kluge A, Miscimarra LE, Cartier KC, Freebairn LA et al. Speech sound disorder influenced by a locus in 15q14 region. Behav Genet 2006; 36: 858-868.
5. Chagnon YC. Shared susceptibility region on chromosome 15 between autism and catatonia. Int Rev Neurobiol 2006; 72: 165-178.
6. Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T et al. Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet 2002; 32: 650-654.
7. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005; 308: 385-389.
8. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005; 6: 95-108.
9. Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet 2005; 6: 109-118.
10. Liu B. Statistical Genomics: Linkage, Mapping, and QTL Analysis. CRC Press: Boca Raton, 1997.
11. Ebmeier K, Rose E, Steele D. Cognitive impairment and fMRI in major depression. Neurotox Res 2006; 10: 87-92.
12. Dickerson BC. Functional MRI in the early detection of dementias. Rev Neurol (Paris) 2006; 162: 941-944.
13. Yurgelun-Todd DA, Ross AJ. Functional magnetic resonance imaging studies in bipolar disorder. CNS Spectr 2006; 11: 287-297.
14. Davis CE, Jeste DV, Eyler LT. Review of longitudinal functional neuroimaging studies of drug treatments in patients with schizophrenia. Schizophr Res 2005; 78: 45-60.
15. Kircher TT, Thienel R. Functional brain imaging of symptoms and cognition in schizophrenia. Prog Brain Res 2005; 150: 299-308.
16. Lawrie SM, Hall J, McIntosh AM, Cunningham-Owens DG, Johnstone EC. Neuroimaging and molecular genetics of schizophrenia: pathophysiological advances and therapeutic potential. Br J Pharmacol 2008; 153(Suppl 1): S120-S124.
17. Turner JA, Smyth P, Macciardi F, Fallon JH, Kennedy JL, Potkin SG. Imaging phenotypes and genotypes in schizophrenia. Neuroinformatics 2006; 4: 21-49.
18. Roffman JL, Weiss AP, Goff DC, Rauch SL, Weinberger DR. Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia. Harv Rev Psychiatry 2006; 14: 78-91.
19. Meyer-Lindenberg A, Zink CF. Imaging genetics for neuropsychiatric disorders. Child Adolesc Psychiatr Clin N Am 2007; 16: 581-597.
20. Glahn DC, Thompson PM, Blangero J. Neuroimaging endophenotypes: strategies for finding genes influencing brain structure and function. Hum Brain Mapp 2007; 28: 488-501.
21. Manoach DS. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 2003; 60: 285-298.
22. Barch DM, Carter CS, Braver TS, Sabb FW, MacDonald III A, Noll DC et al. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Arch Gen Psychiatry 2001; 58: 280-288.
23. Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B et al. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 2003; 160: 709-719.
24. Karlsgodt KH, Glahn DC, van Erp TG, Therman S, Huttunen M, Manninen M et al. The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophr Res 2007; 89: 191-197.
25. Tura E, Turner JA, Fallon JH, Kennedy JL, Potkin SG. Multivariate analyses suggest genetic impacts on neurocircuitry in schizophrenia. Neuroreport 2008; 19: 603-607.
26. Cannon TD, Keller MC. Endophenotypes in the genetic analyses of mental disorders. Annu Rev Clin Psychol 2006; 2: 267-290.
27. Manoach DS, Press DZ, Thangaraj V, Searl MM, Goff DC, Halpern E et al. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry 1999; 45: 1128-1137.
28. Perlstein WM, Carter CS, Noll DC, Cohen JD. Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. Am J Psychiatry 2001; 158: 1105-1113.
29. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E et al. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 2000; 48: 99-109.
30. Akbarian S, Bunney Jr WE, Potkin SG, Wigal SB, Hagman JO, Sandman CA et al. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiatry 1993; 50: 169-177.
31. Papassotiropoulos A, Stephan DA, Huentelman MJ, Hoerndli FJ, Craig DW, Pearson JV et al. Common Kibra alleles are associated with human memory performance. Science 2006; 314: 475-478.
32. Almasy L, Gur RC, Haack K, Cole SA, Calkins ME, Peralta JM et al. A genome screen for quantitative trait loci influencing schizophrenia and neurocognitive phenotypes. Am J Psychiatry 2008; 165: 1185-1192.
33. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917-6922.
34. Meyer-Lindenberg A, Nichols T, Callicott JH, Ding J, Kolachana B, Buckholtz J et al. Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry 2006; 11: 867-877, 797.
35. Glahn DC, Paus T, Thompson PM. Imaging genomics: mapping the influence of genetics on brain structure and function. Hum Brain Mapp 2007; 28: 461-463.
36. de Geus E, Goldberg T, Boomsma DI, Posthuma D. Imaging the genetics of brain structure and function. Biol Psychol 2008; 79: 1-8.
37. Aleman A, Swart M, van Rijn S. Brain imaging, genetics and emotion. Biol Psychol 2008; 79: 58-69.
38. Shaw P, Gornick M, Lerch J, Addington A, Seal J, Greenstein D et al. Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2007; 64: 921-931.
39. van Haren NE, Bakker SC, Kahn RS. Genes and structural brain imaging in schizophrenia. Curr Opin Psychiatry 2008; 21: 161-167.
40. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). Biometrics Research New York State Psychiatric Institute: New York, 2002.
41. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP). Biometrics Research New York State Psychiatric Institute: New York, 2002.
42. Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas CS, Rainey L et al. Automated Talairach atlas labels for functional brain mapping. Hum Brain Mapp 2000; 10: 120-131.
43. Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, DA R. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38: 904-909.
44. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D et al. PLINK: a tool set for whole-genome association and population-based linkage analysis. Am J Hum Genet 2007; 81: 559-575.
45. StataCorp. Stata Statistical Software Release 10. Stata Corporation: College Station, Texas, 2007.
46. Heimer L. Basal forebrain in the context of schizophrenia. Brain Res Brain Res Rev 2000; 31: 205-235.
47. Petrides M. Lateral prefrontal cortex: architectonic and functional organization. Philos Trans R Soc Lond B Biol Sci 2005; 360: 781-795.
48. Fallon JH, Opole IO, Potkin SG. Neuroanatomy of schizophrenia: circuitry and neurotransmitter systems. Clin Neurosci Res 2003; 3: 77-107.
49. Potkin SG, Alva G, Fleming K, Anand R, Keator D, Carreon D et al. A PET study of the pathophysiology of negative symptoms in schizophrenia. Positron emission tomography. Am J Psychiatry 2002; 159: 227-237.
50. Fallon J, Reid S, Kinyamu R, Opole I, Opole R, Baratta J et al. In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci USA 2000; 97: 14686-14691.
51. Nichols T, Hayasaka S. Controlling the familywise error rate in functional neuroimaging: a comparative review. Stat Methods Med Res 2003; 12: 419-446.
52. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B 1995; 57: 289-300.
53. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci USA 2003; 100: 9440-9445.
54. Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004; 74: 765-769.
55. Meng Z, Zaykin DV, Xu CF, Wagner M, Ehm MG. Selection of genetic markers for association analyses, using linkage disequilibrium and haplotypes. Am J Hum Genet 2003; 73: 115-130.
56. Dudbridge F, Gusnanto A, Koeleman BP. Detecting multiple associations in genome-wide studies. Hum Genomics 2006; 2: 310-317.
57. Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet 2006; 7: 781-791.
58. Dudbridge F, Koeleman BP. Efficient computation of significance levels for multiple associations in large studies of correlated data, including genomewide association studies. Am J Hum Genet 2004; 75: 424-435.
59. Kirov G, Zaharieva I, Georgieva L, Moskvina V, Nikolov I, Cichon S et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol Psychiatry 2008; DOI:10.1038/mp.2008.33.
60. Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, Kane JM et al. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psychiatry 2007; 12: 572-580.
61. Mah S, Nelson MR, Delisi LE, Reneland RH, Markward N, James MR et al. Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Mol Psychiatry 2006; 11: 471-478.
62. Shifman S, Johannesson M, Bronstein M, Chen SX, Collier DA, Craddock NJ et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet 2008; 4: e28.
63. Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, Stroup TS et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry 2008; 13: 570-584.
64. Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 2007; 39: 1477-1482.
65. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev 2001; 81: 153-208.
66. Symons M. Rho family GTPases: the cytoskeleton and beyond. Trends Biochem Sci 1996; 21: 178-181.
67. Kozma R, Ahmed S, Best A, Lim L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol Cell Biol 1995; 15: 1942-1952.
68. Wells A. EGF receptor. Int J Biochem Cell Biol 1999; 31: 637-643.
69. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA, Cravchik A et al. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 1997; 43: 1-8.
70. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ et al. Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome Res 2000; 10: 1546-1560.
71. Rakic S, Zecevic N. Early oligodendrocyte progenitor cells in the human fetal telencephalon. Glia 2003; 41: 117-127.
72. Ge D, Zhang K, Need AC, Martin O, Fellay J, Urban TJ et al. WGAViewer: software for genomic annotation of whole genome association studies. Genome Res 2008; 18: 640-643.