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Annual Review of Genomics and Human Genetics

Volume 3, 2002

L A P D: The Emerging Picture

Abstract

▪  

Gene finding in genetically complex diseases has been difficult as a result of many factors that have diagnostic and methodologic considerations. For bipolar disorder and schizophrenia, numerous family, twin, and adoption studies have identified a strong genetic component to these behavioral psychiatric disorders. Despite difficulties that include diagnostic differences between sample populations and the lack of statistical significance in many individual studies, several promising patterns have emerged, suggesting that true susceptibility loci for schizophrenia and bipolar disorder may have been identified. In this review, the genetic epidemiology of these disorders is covered as well as linkage findings on chromosomes 4, 12, 13, 18, 21, and 22 in bipolar disorder and on chromosomes 1, 6, 8, 10, 13, 15, and 22 in schizophrenia. The sequencing of the human genome and identification of numerous single nucleotide polymorphisms (SNP) should substantially enhance the ability of investigators to identify disease-causing genes in these areas of the genome.

Keyword(s): bipolar disorder, candidate gene, complex genetic disease, genomics, linkage disequilibrium, schizophrenia
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/content/journals/10.1146/annurev.genom.3.022502.103141
2002-09-01
2024-05-18
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Literature Cited

  1. Aita VM, Liu J, Knowles JA, Terwilliger JD, Baltazar R. et al. 1999. A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective disorder locus.. Am. J. Hum. Genet. 64:210–17 [Google Scholar]
  2. Allen MG, Cohen S, Pollin W, Greenspan SI. 1974. Affective illness in veteran twins: a diagnostic review.. Am. J. Psychiatry 131:1234–39 [Google Scholar]
  3. Altshuler D, Pollara VJ, Cowles CR, Van Etten WJ, Baldwin J. et al. 2000. An SNP map of the human genome generated by reduced representation shotgun sequencing.. Nature 407:513–16 [Google Scholar]
  4. Am. Psychiatr. Assoc 1987. Diagnostic and Statistical Manual of Mental Disorder. Washington, DC: Am. Psychiatr. Assoc. 3rd ed. revis [Google Scholar]
  5. Am. Psychiatr. Assoc 1994. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am. Psychiatr. Assoc. 4th ed [Google Scholar]
  6. Asherson P, Mant R, Williams N, Cardno A, Jones L. et al. 1998. A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.. Mol. Psychiatry 3:310–20 [Google Scholar]
  7. Badenhop RF, Moses MJ, Scimone A, Mitchell PB, Ewen KR. et al. 2001. A genome screen of a large bipolar affective disorder pedigree supports evidence for a susceptibility locus on chromosome 13q.. Mol. Psychiatry 6:396–403 [Google Scholar]
  8. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U. et al. 2000. Genome scan for susceptibility loci for schizophrenia.. Neuropsychobiology 42:175–82 [Google Scholar]
  9. Baron M. 2001. Genetics of schizophrenia and the new millennium: progress and pitfalls.. Am. J. Hum. Genet. 68:299–312 [Google Scholar]
  10. Baron M, Knowles JA. 1999. Chromosome 18p11 and linkage to bipolar disorder revisited.. Psychiatr. Genet. 9:201–3 [Google Scholar]
  11. Baron M, Knowles JA. 2000. Bipolar disorder and chromosome 18p11: uncertainties redux.. Psychiatr. Genet. 10:55–58 [Google Scholar]
  12. Bassett AS, Chow EW, Weksberg R. 2000. Chromosomal abnormalities and schizophrenia.. Am. J. Med. Genet. 97:45–51 [Google Scholar]
  13. Bennett P, Middle F, Mulcahy T, Jones I, McCandless F. et al. 1999. The Wellcome Trust UK–Irish bipolar sib-pair study.. Mol. Psychiatry 4 (Suppl. 1):S21 [Google Scholar]
  14. Berrettini WH. 1999. Response to Baron and Knowles.. Psychiatr. Genet. 9:205–6 [Google Scholar]
  15. Berrettini WH. 2000. Genetics of psychiatric disease.. Annu. Rev. Med. 51:465–79 [Google Scholar]
  16. Berrettini WH, Ferraro TN, Goldin LR, Detera-Wadleigh SD, Choi H. et al. 1997. A linkage study of bipolar illness.. Arch. Gen. Psychiatry 54:27–35 [Google Scholar]
  17. Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S. et al. 1994. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.. Proc. Natl. Acad. Sci. USA 91:5918–21 [Google Scholar]
  18. Deleted in proof
  19. Berrettini WH, Vuoristo J, Ferraro TN, Buono RJ, Wildenauer D. et al. 1998. Human G(olf) gene polymorphisms and vulnerability to bipolar disorder.. Psychiatr. Genet. 8:235–38 [Google Scholar]
  20. Bertelson A, Harvald B, Haruge M. 1977. A Danish twin study of manic-depressive illness.. Br. J. Psychiatry 130:330–51 [Google Scholar]
  21. Blackwood DH, He L, Morris SW, McLean A, Whitton C. et al. 1996. A locus for bipolar affective disorder on chromosome 4p.. Nat. Genet. 12:427–30 [Google Scholar]
  22. Blouin JL, Dombroski BA, Nath SK, Lasseter VK, Wolyniec PS. et al. 1998. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.. Nat. Genet. 20:70–73 [Google Scholar]
  23. Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett AS. 2000. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22.. Science 288:678–82 [Google Scholar]
  24. Brzustowicz LM, Honer WG, Chow EW, Little D, Hogan J. et al. 1999. Linkage of familial schizophrenia to chromosome 13q32.. Am. J. Hum. Genet. 65:1096–103 [Google Scholar]
  25. Byerley W, Holik J, Hoff M, Coon H. 1995. Search for a gene predisposing to manic depression on chromosome 21.. Am. J. Med. Genet. 60:231–33 [Google Scholar]
  26. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA. et al. 1997. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees.. Genomics 43:1–8 [Google Scholar]
  27. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR. et al. 1999. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.. Arch. Gen. Psychiatry 56:162–68 [Google Scholar]
  28. Chandy KG, Fantino E, Wittekindt O, Kalman K, Tong LL. et al. 1998. Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?. Mol. Psychiatry 3:32–37 [Google Scholar]
  29. Chen H, Huo Y, Patel S, Zhu X, Swift-Scanlan T. et al. 2000. Gene identification using exon amplification on human chromosome 18q21: implications for bipolar disorder.. Mol. Psychiatry 5:502–9 [Google Scholar]
  30. Cichon S, Schmidt-Wolf G, Putzstuck M, Hemmer S, Albus M. et al. 1999. Systematic search for susceptibility genes in bipolar affective disorder: evidence for a disease locus at 10q26.. Mol. Psychiatry 4:S19 [Google Scholar]
  31. Consort. Inst. Hered. Genealol. Stud 2001. Initial sequencing and analysis of the human genome.. Nature 406:860–921 [Google Scholar]
  32. Coon H, Hoff M, Holik J, Hadley D, Fang N. et al. 1996. Analysis of chromosome 18 DNA markers in multiplex pedigrees with manic depression.. Biol. Psychiatry 39:689–96 [Google Scholar]
  33. Coon H, Jensen S, Hoff M, Holik J, Plaetke R. et al. 1993. A genome-wide search for genes predisposing to manic depression, assuming autosomal dominant inheritance.. Am. J. Hum. Genet. 6:1234–49 [Google Scholar]
  34. Coon H, Jensen S, Holik J, Hoff M, Myles-Worsley M. et al. 1994. Genomic scan for genes predisposing to schizophrenia.. Am. J. Med. Genet. 54:59–71 [Google Scholar]
  35. Coon H, Myles-Worsley M, Tiobech J, Hoff M, Rosenthal J. et al. 1998. Evidence for a chromosome 2p13-14 schizophrenia susceptibility locus in families from Palau, Micronesia.. Mol. Psychiatry 3:521–27 [Google Scholar]
  36. Coon H, Plaetke R, Holik J, Hoff M, Myles-Worsley M. et al. 1993. Use of a neurophysiological trait in linkage analysis of schizophrenia.. Biol. Psychiatry 34:277–89 [Google Scholar]
  37. Craddock N, Owen M, Burge S, Kurian B, Thomas P. et al. 1994. Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis).. Br. J. Psychiatry 164:355–58 [Google Scholar]
  38. Crawford TJ, Sharma T, Puri BK, Murray RM, Berridge DM. et al. 1998. Saccadic eye movements in families multiply when affected with schizophrenia: the Maudsley Family Study.. Am. J. Psychiatry 155:1703–10 [Google Scholar]
  39. Daly M, Kirby A, Kruglyak L. 1997. Do multiple data sets provide support for a bipolar illness susceptibility locus on chromosome 18?. Genet. Epidemiol. 14:599–604 [Google Scholar]
  40. Dawson E, Chen Y, Hunt S, Smink LJ, Hunt A. et al. 2001. An SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.. Genome Res. 11:170–78 [Google Scholar]
  41. Dawson E, Gill M, Curtis D, Castle D, Hunt N. et al. 1995. Genetic association between alleles of pancreatic phospholipase A2 gene and bipolar affective disorder.. Psychiatr. Genet. 5:177–80 [Google Scholar]
  42. De Bruyn A, Souery D, Mendelbaum K, Mendlewicz J, Van Broeckhoven C. 1996. Linkage analysis of families with bipolar illness and chromosome 18 markers.. Biol. Psychiatry 39:679–88 [Google Scholar]
  43. de la Chapelle A, Wright FA. 1998. Linkage disequilibrium mapping in isolated populations: the example of Finland revisited.. Proc. Natl. Acad. Sci. USA 95:12416–23 [Google Scholar]
  44. DeLisi LE, Craddock NJ, Detera-Wadleigh S, Foroud T, Gejman P. et al. 2000. Update on chromosomal locations for psychiatric disorders: report of the interim meeting of chromosome workshop chairpersons from the VIIth World Congress of Psychiatric Genetics, Monterey, California, October 14–18, 1999.. Am. J. Med. Genet. 96:434–49 [Google Scholar]
  45. DeLisi LE, Crow TJ. 1999. Chromosome workshops 1998: current state of psychiatric linkage.. Am. J. Med. Genet. 88:215–18 [Google Scholar]
  46. Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin LR. et al. 1999. A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2.. Proc. Natl. Acad. Sci. USA 96:5604–9 [Google Scholar]
  47. Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR. et al. 1996. Affected sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder on 21q.. Am. J. Hum. Genet. 58:1279–85 [Google Scholar]
  48. Detera-Wadleigh SD, Badner JA, Yoshikawa T, Sanders AR, Goldin LR. et al. 1997. Initial genome scan of the NIMH Genetics Initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q.. Am. J. Med. Genet. 74:254–62 [Google Scholar]
  49. Deutsch S, Iseli C, Bucher P, Antonarakis SE, Scott HS. 2001. A cSNP map and database for human chromosome 21.. Genome Res. 11:300–7 [Google Scholar]
  50. Dorr DA, Rice JP, Armstrong C, Reich T, Blehar M. 1997. A meta-analysis of chromosome 18 linkage data for bipolar illness.. Genet. Epidemiol. 14:617–22 [Google Scholar]
  51. Durner M, Abreu P. 1997. Exploring linkage of chromosome 18 markers and bipolar disease.. Genet. Epidemiol. 14:623–27 [Google Scholar]
  52. Edenberg HJ, Foroud T, Conneally PM, Sorbel JJ, Carr K. et al. 1997. Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.. Am. J. Med. Genet. 74:238–46 [Google Scholar]
  53. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK. et al. 1987. Bipolar affective disorders linked to DNA markers on chromosome 11.. Nature 325:783–87 [Google Scholar]
  54. Ekelund J, Lichtermann D, Hovatta I, Ellonen P, Suvisaari J. et al. 2000. Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22.. Hum. Mol. Genet. 9:1049–57 [Google Scholar]
  55. Engert JC, Berube P, Mercier J, Dore C, Lepage P. et al. 2000. ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5 kb ORF.. Nat. Genet. 24:120–25 [Google Scholar]
  56. Evans KL, Le Hellard S, Morris SW, Lawson D, Whitton C. et al. 2001. A 6.9-mb high-resolution bac/pac contig of human 4p15.3-p16.1, a candidate region for bipolar affective disorder.. Genomics 71:315–23 [Google Scholar]
  57. Ewald H, Degn B, Mors O, Kruse TA. 1998. Significant linkage between bipolar affective disorder and chromosome 12q24.. Psychiatr. Genet. 8:131–40 [Google Scholar]
  58. Ewald H, Degn B, Mors O, Kruse TA. 1998. Support for the possible locus on chromosome 4p16 for bipolar affective disorder.. Mol. Psychiatry 3:442–48 [Google Scholar]
  59. Ewald H, Eiberg H, Mors O, Flint T, Kruse TA. 1996. Linkage study between manic-depressive illness and chromosome 21.. Am. J. Med. Genet. 67:218–24 [Google Scholar]
  60. Faraone SV, Blehar M, Pepple J, Moldin SO, Norton J. et al. 1996. Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.. Psychol. Med. 26:401–10 [Google Scholar]
  61. Faraone SV, Matise T, Svrakic D, Pepple J, Malaspina D. et al. 1998. Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.. Am. J. Med. Genet. 81:290–95 [Google Scholar]
  62. Farmer AE, McGuffin P, Gottesman I. 1987. Twin concordance for DSM-III schizophrenia.. Scrutinizing the validity of the definition Arch. Gen. Psychiatry 44:634–41 [Google Scholar]
  63. Fogelson DL, Nuechterlein KH, Asarnow RF, Subotnik KL, Talovic SA. 1991. Interrater reliability of the Structured Clinical Interview for DSM-III-R, Axis II: schizophrenia spectrum and affective spectrum disorders.. Psychiatry Res. 39:55–63 [Google Scholar]
  64. Foroud T, Castelluccio PF, Koller DL, Edenberg HJ, Miller M. et al. 2000. Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees.. Am. J. Med. Genet. 96:18–23 [Google Scholar]
  65. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A. et al. 1997. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.. Proc. Natl. Acad. Sci. USA 94:587–92 [Google Scholar]
  66. Freimer NB, Reus VI, Escamilla MA, McInnes LA, Spesny M. et al. 1996. Genetic mapping using haplotype, association, and linkage methods suggests a locus for severe bipolar disorder (BP I) at 18q22-q23.. Nat. Genet. 12:436–41 [Google Scholar]
  67. Freimer NB, Reus VI, Escamilla M, Spesny M, Smith L. et al. 1996. An approach to investigating linkage for bipolar disorder using large Costa Rican pedigrees.. Am. J. Med. Genet. 67:254–63 [Google Scholar]
  68. Friddle C, Koskela R, Ranade K, Hebert J, Cargill M. et al. 2000. Full-genome scan for linkage in 50 families segregating the bipolar affective disease phenotype.. Am. J. Hum. Genet. 66:205–15 [Google Scholar]
  69. Gershon ES. 2000. Bipolar illness and schizophrenia as oligogenic diseases: implications for the future.. Biol. Psychiatry 47:240–44 [Google Scholar]
  70. Gershon ES, Badner JA, Detera-Wadleigh SD, Ferraro TN, Berrettini WH. 1996. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees.. Am. J. Med. Genet. 67:202–7 [Google Scholar]
  71. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF. et al. 1982. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands.. Arch. Gen. Psychiatry 39:1157–67 [Google Scholar]
  72. Gershon ES, Mark A, Cohen N, Belizon N, Baron M. et al. 1975. Transmitted factors in the morbid risk of affective disorders: a controlled study.. J. Psychiatr. Res. 12:283–99 [Google Scholar]
  73. Ginns EI, Ott J, Egeland JA, Allen CR, Fann CS. et al. 1996. A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish.. Nat. Genet. 12:431–35 [Google Scholar]
  74. Gogos JA, Morgan M, Luine V, Santha M, Ogawa S. et al. 1998. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior.. Proc. Natl. Acad. Sci. USA 95:9991–96 [Google Scholar]
  75. Gogos JA, Santha M, Takacs Z, Beck KD, Luine V. et al. 1999. The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.. Nat. Genet. 21:434–39 [Google Scholar]
  76. Goldgar DE, Easton DF. 1997. Optimal strategies for mapping complex diseases in the presence of multiple loci.. Am. J. Hum. Genet. 60:1222–32 [Google Scholar]
  77. Gottesman II. 1991. Schizophrenia Genesis: The Origins of Madness. New York: WH Freeman [Google Scholar]
  78. Greenberg DA, Hodge SE, Vieland VJ, Spence MA. 1998. Power, mode of inheritance, and type I error in LOD scores and affecteds-only methods: reply to Kruglyak.. Am. J. Hum. Genet. 62:202–4 [Google Scholar]
  79. Gurling H, Kalsi G, Brynjolfson J, Sigmundsson T, Sherrington R. et al. 2001. Genome-wide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia on chromosomes 11q23.3-24 and 20q12.1-11.23.. Am. J. Hum. Genet. 68:661–73 [Google Scholar]
  80. Gurling H, Smyth C, Kalsi G, Moloney E, Rifkin L. et al. 1995. Linkage findings in bipolar disorder.. Nat. Genet. 10:8–9 [Google Scholar]
  81. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T. et al. 2000. The DNA sequence of human chromosome 21.. The Chromosome 21 Mapping and Sequencing Consortium Nature 405:311–19 [Google Scholar]
  82. Heun R, Maier W. 1993. The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: results of a controlled family study.. Acta Psychiatr. Scand. 87:279–84 [Google Scholar]
  83. Hodge SE, Abreu PC, Greenberg DA. 1997. Magnitude of type I error when single-locus linkage analysis is maximized over models: a simulation study.. Am. J. Hum. Genet. 60:217–27 [Google Scholar]
  84. Holzman PS, Kringlen E, Matthysse S, Flanagan SD, Lipton RB. et al. 1988. A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins.. Arch. Gen. Psychiatry 45:641–47 [Google Scholar]
  85. Hovatta I, Varilo T, Suvisaari J, Terwilliger JD, Ollikainen V. et al. 1999. A genome-wide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci.. Am. J. Hum. Genet. 65:1114–24 [Google Scholar]
  86. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP. et al. 2001. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.. Nature 411:599–603 [Google Scholar]
  87. Jacobsen N, Daniels J, Moorhead S, Harrison D, Feldman E. et al. 1996. Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1.. Psychiatr. Genet. 6:195–99 [Google Scholar]
  88. Jacobsen NJ, Franks EK, Owen MJ, Craddock NJ. 1999. Mutational analysis of phospholipase A2A: a positional candidate susceptibility gene for bipolar disorder.. Mol. Psychiatry 4:274–79 [Google Scholar]
  89. Jacobsen NJ, Lyons I, Hoogendoorn B, Burge S, Kwok P-Y. et al. 1999. ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes.. Hum. Mol. Genet. 8:1631–36 [Google Scholar]
  90. Jerome LA, Papaioannou VE. 2001. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.. Nat. Genet. 27:286–91 [Google Scholar]
  91. Jorde LB, Watkins WS, Kere J, Nyman D, Eriksson AW. 2000. Gene mapping in isolated populations: new roles for old friends?. Hum. Hered. 50:57–65 [Google Scholar]
  92. Judd LL, McAdams L, Budnick B, Braff DL. 1992. Sensory-gating deficits in schizophrenia: new results.. Am. J. Psychiatry 149:488–93 [Google Scholar]
  93. Kalsi G, Mankoo B, Curtis D, Sherrington R, Melmer G. et al. 1999. New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families.. Ann. Hum. Genet. 63:235–47 [Google Scholar]
  94. Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R. et al. 1995. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.. Proc. Natl. Acad. Sci. USA 92:7612–16 [Google Scholar]
  95. Katsanis J, Taylor J, Iacono WG, Hammer MA. 2000. Heritability of different measures of smooth pursuit eye tracking dysfunction: a study of normal twins.. Psychophysiology 6:724–30 [Google Scholar]
  96. Kaufmann CA, Suarez B, Malaspina D, Pepple J, Svrakic D. et al. 1998. NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.. Am. J. Med. Genet. 81:282–89 [Google Scholar]
  97. Kelsoe JR, Spence MA, Loetscher E, Foguet M, Sadovnick AD. et al. 2001. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22.. Proc. Natl. Acad. Sci. USA 98:585–90 [Google Scholar]
  98. Kendler KS, Karkowski LM, Walsh D. 1998. The structure of psychosis: latent class analysis of probands from the Roscommon Family Study.. Arch. Genet. Psychiatry 55:492–99 [Google Scholar]
  99. Kendler KS, MacLean CJ, O'Neill FA, Burke J, Murphy B. et al. 1996. Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.. Am. J. Psychiatry 153:1534–40 [Google Scholar]
  100. Kendler KS, Pedersen N, Johnson L, Neale MC, Mathe AA. 1993. A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples.. Arch. Gen. Psychiatry 50:699–700 [Google Scholar]
  101. Kendler KS, Robinette CD. 1983. Schizophrenia in the National Academy of Sciences National Research Council Twin Registry: a 16-year update.. Am. J. Psychiatry 140:1551–63 [Google Scholar]
  102. Knowles JA, Rao PA, Cox-Matise T, Loth JE, de Jesus GM. et al. 1998. No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees.. Am. J. Hum. Genet. 62:916–24 [Google Scholar]
  103. Kruglyak L. 1997. Nonparametric linkage tests are model free.. Am. J. Hum. Genet. 61:254–55 [Google Scholar]
  104. Lachman HM, Kelsoe JR, Remick RA, Sadovnick AD, Rapaport MH. et al. 1997. Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22.. Am. J. Med. Genet. 74:121–28 [Google Scholar]
  105. Lander ES, Kruglyak L. 1995. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.. Nat. Genet. 11:241–47 [Google Scholar]
  106. Leonard S, Adams C, Breese CR, Adler LE, Bickford P. et al. 1996. Nicotinic receptor function in schizophrenia.. Schizophr. Bull. 22:431–45 [Google Scholar]
  107. Levinson DF, Holmans P, Straub RE, Owen MJ, Wildenauer DB. et al. 2000. Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: Schizophrenia Linkage Collaborative Group III.. Am. J. Hum. Genet. 67:652–63 [Google Scholar]
  108. Levinson DF, Mahtani MM, Nancarrow DJ, Brown DM, Kruglyak L. et al. 1998. Genome scan of schizophrenia.. Am. J. Psychiatry 155:741–50 [Google Scholar]
  109. Li H, Schaid DJ. 1997. Genehunter: application to analysis of bipolar pedigrees and some extensions.. Genet. Epidemiol. 14:659–63 [Google Scholar]
  110. Lin JP, Bale SJ. 1997. Parental transmission and D18S37 allele sharing in bipolar affective disorder.. Genet. Epidemiol. 6:665–68 [Google Scholar]
  111. Lin MW, Curtis D, Williams N, Arranz M, Nanko S. et al. 1995. Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32.. Psychiatr. Genet. 5:117–26 [Google Scholar]
  112. Lin MW, Sham P, Hwu HG, Collier D, Murray R. et al. 1997. Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations.. Hum. Genet. 99:417–20 [Google Scholar]
  113. MacKinnon DF, Xu J, McMahon FJ, Simpson SG, Stine OC. et al. 1998. Bipolar disorder and panic disorder in families: an analysis of chromosome 18 data.. Am. J. Psychiatry 155:829–31 [Google Scholar]
  114. Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R. et al. 1993. Continuity and discontinuity of affective disorders and schizophrenia.. Results of a controlled family study Arch. Gen. Psychiatry 50:871–83 [Google Scholar]
  115. Martinez M, Goldin LR, Cao QH, Zhang J, Sanders AR. et al. 1999. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q.. Am. J. Med. Genet. 88:337–43 [Google Scholar]
  116. Maziade M, Roy MA, Rouillard E, Bissonnette L, Fournier JP. et al. 2001. A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes.. Mol. Psychiatry 6:684–93 [Google Scholar]
  117. McInnes LA, Escamilla MA, Service SK, Reus VI, Leon P. et al. 1996. A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.. Proc. Natl. Acad. Sci. USA 93:13060–65 [Google Scholar]
  118. McMahon FJ, Hopkins PJ, Xu J, McInnis MG, Shaw S. et al. 1997. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series.. Am. J. Hum. Genet. 61:1397–404 [Google Scholar]
  119. Merscher S, Funke B, Epstein JA, Heyer J, Puech A. et al. 2001. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.. Cell 104:619–29 [Google Scholar]
  120. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS. et al. 2000. Disruption of two novel genes by a translocation cosegregating with schizophrenia.. Hum. Mol. Genet. 9:1415–23 [Google Scholar]
  121. Moises HW, Yang L, Kristbjarnarson H, Wiese C, Byerley W. et al. 1995. An international two-stage genome-wide search for schizophrenia susceptibility genes.. Nat. Genet. 11:321–24 [Google Scholar]
  122. Morissette J, Villeneuve A, Bordeleau L, Rochette D, Laberge C. et al. 1999. Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in Quebec points to a locus of major effect on chromosome 12q23-q24.. Am. J. Med. Genet. 88:567–87 [Google Scholar]
  123. Morton NE. 1995. Sequential tests for the detection of linkage.. Am. J. Hum. Genet. 7:277–318 [Google Scholar]
  124. Mullikin JC, Hunt SE, Cole CG, Mortimore BJ, Rice CM. et al. 2000. An SNP map of human chromosome 22.. Nature 407:516–20 [Google Scholar]
  125. Nathan PE, Langenbucher JW. 1999. Psychopathology: description and classification.. Annu. Rev. Psychol. 50:79–107 [Google Scholar]
  126. Natl. Inst. Ment. Health 1997. Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a preliminary report.. Am. J. Med. Genet. 74:227–37 [Google Scholar]
  127. Nothen MM, Cichon S, Rohleder H, Hemmer S, Franzek E. et al. 1999. Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.. Mol. Psychiatry 4:76–84 [Google Scholar]
  128. O'Donovan MC, Owen MJ. 1999. Candidate-gene association studies of schizophrenia.. Am. J. Hum. Genet. 65:587–92 [Google Scholar]
  129. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF. et al. 2001. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.. Nature 411:603–6 [Google Scholar]
  130. Onstad S, Skre I, Torgersen S, Kringlen E. 1991. Twin concordance for DSM-III-R schizophrenia.. Acta Psychiatr. Scand. 83:395–401 [Google Scholar]
  131. Ozelius LJ, Kramer PL, de Leon D, Risch N, Bressman SB. et al. 1992. Strong allelic association between the torsion dystonia gene (DYT1) and loci on chromosome 9q34 in Ashkenazi Jews.. Am. J. Hum. Genet. 50:619–28 [Google Scholar]
  132. Pauls DL, Morton LA, Egeland JA. 1992. Risks of affective illness among first-degree relatives of bipolar I Old-Order Amish probands.. Arch. Gen. Psychiatry 49:703–8 [Google Scholar]
  133. Peltonen L. 2000. Positional cloning of disease genes: advantages of genetic isolates.. Hum. Hered. 50:66–75 [Google Scholar]
  134. Peltonen L, Jalanko A, Varilo T. 1999. Molecular genetics of the Finnish disease heritage.. Hum. Mol. Genet. 8:1913–23 [Google Scholar]
  135. Pericak-Vance MA, Bebout JL, Gaskell PC Jr, Yamaoka LH, Hung WY. et al. 1991. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.. Am. J. Hum. Genet. 48:1034–50 [Google Scholar]
  136. Pollin W, Allen MG, Hoffer A, Stabenau JR, Hrubec Z. 1969. Psychopathology in 15,909 pairs of veteran twins: evidence for a genetic factor in the pathogenesis of schizophrenia and its relative absence in psychoneurosis.. Am. J. Psychiatry 126:597–610 [Google Scholar]
  137. Polymeropoulos MH, Coon H, Byerley W, Gershon ES, Goldin L. et al. 1994. Search for a schizophrenia susceptibility locus on human chromosome 22.. Am. J. Med. Genet. 54:93–99 [Google Scholar]
  138. Prescott CA, Gottesman I. 1993. Genetically mediated vulnerability to schizophrenia.. Psychiatr. Clin. N. Am. 16:245–67 [Google Scholar]
  139. Pulver AE. 2000. Search for schizophrenia susceptibility genes.. Biol. Psychiatry 47:221–30 [Google Scholar]
  140. Pulver AE, Karayiorgou M, Lasseter VK, Wolyniec P, Kasch L. et al. 1994. Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13.1: part 2.. Am. J. Med. Genet. 54:44–50 [Google Scholar]
  141. Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L. et al. 1994. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: part 1.. Am. J. Med. Genet. 54:36–43 [Google Scholar]
  142. Pulver AE, Lasseter VK, Kasch L, Wolyniec P, Nestadt G. et al. 1995. Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes.. Am. J. Med. Genet. 60:252–60 [Google Scholar]
  143. Pulver AE, Mulle J, Nestadt G, Swartz KL, Blouin JL. et al. 2000. Genetic heterogeneity in schizophrenia: stratification of genome-scan data using cosegregating related phenotypes.. Mol. Psychiatry 5:650–53 [Google Scholar]
  144. Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M. et al. 1994. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.. J. Nerv. Ment. Dis. 182:476–78 [Google Scholar]
  145. Rees MI, Fenton I, Williams NM, Holmans P, Norton N. et al. 1999. Autosome search for schizophrenia susceptibility genes in multiply affected families.. Mol. Psychiatry 4:353–59 [Google Scholar]
  146. Rice J, Reich T, Andreasen NC, Endicott J, Van Eerdewegh M. et al. 1987. The familial transmission of bipolar illness.. Arch. Gen. Psychiatry 44:441–47 [Google Scholar]
  147. Rice JP, Goate A, Williams JT, Bierut L, Dorr D. et al. 1997. Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12.. Am. J. Med. Genet. 74:247–53 [Google Scholar]
  148. Rice JP, McDonald-Scott P, Endicott J, Coryell W, Grove WM. et al. 1986. The stability of diagnosis with an application to bipolar II disorder.. Psychiatr. Res. 19:285–96 [Google Scholar]
  149. Riley BP, Rajagopalan S, Mogudi-Carter M, Jenkins T, Williamson R. 1996. No evidence for linkage of chromosome 6p markers to schizophrenia in southern African Bantu-speaking families.. Psychiatr. Genet. 6:41–49 [Google Scholar]
  150. Rojas K, Liang L, Johnson EI, Berrettini WH, Overhauser J. 2000. Identification of candidate genes for psychiatric disorders on 18p11.. Mol. Psychiatry 5:389–95 [Google Scholar]
  151. Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S. et al. 1999. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.. Nat. Genet. 21:271–77 [Google Scholar]
  152. Schizophr. Link. Collab. Group Chromosomes 3, 6, 8 1996. Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study.. Am. J. Med. Genet. 67:580–94 [Google Scholar]
  153. Schwab SG, Albus M, Hallmayer J, Honig S, Borrmann M. et al. 1995. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.. Nat. Genet. 11:325–27 [Google Scholar]
  154. Schwab SG, Hallmayer J, Albus M, Lerer B, Eckstein GN. et al. 2000. A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6.. Mol. Psychiatry 5:638–49 [Google Scholar]
  155. Schwab SG, Hallmayer J, Albus M, Lerer B, Hanses C. et al. 1998. Further evidence for a susceptibility locus on chromosome 10p14-p11 in 72 families with schizophrenia by nonparametric linkage analysis.. Am. J. Med. Genet. 81:302–7 [Google Scholar]
  156. Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ. et al. 1998. A genome-wide search for schizophrenia susceptibility genes.. Am. J. Med. Genet. 81:364–76 [Google Scholar]
  157. Sherrington R, Brynjolfsson J, Petursson H, Potter M, Dudleston K. et al. 1988. Localization of a susceptibility locus for schizophrenia on chromosome 5.. Nature 336:164–67 [Google Scholar]
  158. Sjoholt G, Gulbrandsen AK, Lovlie R, Berle JO, Molven A. et al. 2000. A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients.. Mol. Psychiatry 5:172–80 [Google Scholar]
  159. Sklar P, Sibylle G, Schwab SG, Williams NM, Daly M. et al. 2001. Association analysis of NOTCH4 loci in schizophrenia using family- and population-based controls.. Nat. Genet. 28:126–28 [Google Scholar]
  160. St Clair D, Blackwood D, Muir W, Carothers A, Walker M. et al. 1990. Association within a family of a balanced autosomal translocation with major mental illness.. Lancet 336:13–16 [Google Scholar]
  161. Stine OC, McMahon FJ, Chen L, Xu J, Meyers DA. et al. 1997. Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.. Am. J. Med. Genet. 74:263–69 [Google Scholar]
  162. Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M. et al. 1995. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect.. Am. J. Hum. Genet. 57:1384–94 [Google Scholar]
  163. Stober G, Saar K, Ruschendorf F, Meyer J, Nurnberg G. et al. 2000. Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15.. Am. J. Hum. Genet. 67:1201–7 [Google Scholar]
  164. Straub RE, Lehner T, Luo Y, Loth JE, Shao W. et al. 1994. A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.. Nat. Genet. 8:291–96 [Google Scholar]
  165. Straub RE, MacLean CJ, O'Neill FA, Burke J, Murphy B. et al. 1995. A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity.. Nat. Genet. 11:287–93 [Google Scholar]
  166. Straub RE, MacLean CJ, O'Neill FA, Walsh D, Kendler KS. 1997. Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families.. Mol. Psychiatry 2:148–55 [Google Scholar]
  167. Strober M. 1992. Relevance of early age-of-onset in genetic studies of bipolar affective disorder.. J. Am. Acad. Child Adolesc. Psychiatry 31:606–10 [Google Scholar]
  168. Terwilliger JD, Weiss KM. 1998. Linkage disequilibrium mapping of complex disease: fantasy or reality?. Curr. Opin. Biotechnol. 9:578–94 [Google Scholar]
  169. Tienari P. 1971. Schizophrenia and monozygotic twins.. Vestn. Akad. Med. Nauk. SSSR 26:53–57 [Google Scholar]
  170. Torgersen S. 1986. Genetic factors in moderately severe and mild affective disorders.. Arch. Gen. Psychiatry 43:222–26 [Google Scholar]
  171. Toyota T, Watanabe A, Shibuya H, Nankai M, Hattori E. et al. 2000. Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer–based melting curve analysis on the Light Cycler.. Mol. Psychiatry 5:489–94 [Google Scholar]
  172. Tsuang MT, Stone WS, Faraone SV. 1999. Schizophrenia: a review of genetic studies.. Harv. Rev. Psychiatry 7:185–207 [Google Scholar]
  173. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ. et al. 2001. The sequence of the human genome.. Science 291:1304–51 [Google Scholar]
  174. Vieland VJ, Hodge SE, Greenberg DA. 1992. Adequacy of single-locus approximations for linkage analyses of oligogenic traits.. Genet. Epidemiol. 9:45–59 [Google Scholar]
  175. Vuoristo JT, Berrettini WH, Overhauser J, Prockop DJ, Ferraro TN. et al. 2000. Sequence and genomic organization of the human G-protein Golfalpha gene (GNAL) on chromosome 18p11, a susceptibility region for bipolar disorder and schizophrenia.. Mol. Psychiatry 5:495–501 [Google Scholar]
  176. Wang S, Sun CE, Walczak CA, Ziegle JS, Kipps BR. et al. 1995. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22.. Nat. Genet. 10:41–46 [Google Scholar]
  177. Wei J, Hemmings GP. 2000. Searching for a locus for schizophrenia within chromosome Xp11.. Am. J. Med. Genet. 96:4–7 [Google Scholar]
  178. Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF. et al. 1984. Psychiatric disorders in the relatives of probands with affective disorders.. The Yale University–National Institute of Mental Health Collaborative Study Arch. Gen. Psychiatry 41:13–21 [Google Scholar]
  179. Weissman MM, Leaf PJ, Tischler GL, Blazer DG, Karno M. et al. 1988. Affective disorders in five United States communities.. Psychol. Med. 18:141–53 [Google Scholar]
  180. Williams NM, Rees MI, Holmans P, Norton N, Cardno AG. et al. 1999. A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.. Hum. Mol. Genet. 8:1729–39 [Google Scholar]
  181. Winokur G, Tsuang MT, Crowe RR. 1982. The Iowa 500: affective disorder in relatives of manic and depressed patients.. Am. J. Psychiatry 139:209–12 [Google Scholar]
  182. Yoshikawa T, Sanders AR, Esterling LE, Overhauser J, Garnes JA. et al. 1997. Isolation of chromosome 18–specific brain transcripts as positional candidates for bipolar disorder.. Am. J. Med. Genet. 74:140–49 [Google Scholar]
  183. Young DA, Waldo M, Rutledge JH. Freedman R. 3rd 1996. Heritability of inhibitory gating of the P50 auditory-evoked potential in monozygotic and dizygotic twins.. Neuropsychobiology 33:113–17 [Google Scholar]
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LINKAGE ANALYSIS IN PSYCHIATRIC DISORDERS: The Emerging Picture
Annual Review of Genomics and Human Genetics 3, 371 (2002); https://doi.org/10.1146/annurev.genom.3.022502.103141
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