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J Psychiatry Neurosci. 1999 March; 24(2): 159–165.
PMCID: PMC1188998

Heterogeneity and the genetics of autism.


The objective of this review is to summarize recent data on the genetics of autism, highlight the evidence for genetic heterogeneity and extend the implications of these findings for the identification of susceptibility genes in this disorder. Family studies have shown that autism runs in families and twin studies indicate that the basis of that familial aggregation is genetic. As a result the prospects for the identification of susceptibility genes using either linkage or association studies are quite good. However, recent evidence is accumulating suggesting that the disorder is genetically heterogeneous; higher functioning individuals with autism may arise from separate genetic mechanisms that lower functioning ones. If true, this will make the detection of linkage and association much more difficult.

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Selected References

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  • Hanson DR, Gottesman II. The genetics, if any, of infantile autism and childhood schizophrenia. J Autism Child Schizophr. 1976 Sep;6(3):209–234. [PubMed]
  • Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry. 1977 Sep;18(4):297–321. [PubMed]
  • Tsai LY. Is Rett syndrome a subtype of pervasive developmental disorders? J Autism Dev Disord. 1992 Dec;22(4):551–561. [PubMed]
  • Volkmar FR. Childhood disintegrative disorder: issues for DSM-IV. J Autism Dev Disord. 1992 Dec;22(4):625–642. [PubMed]
  • Szatmari P. The validity of autistic spectrum disorders: a literature review. J Autism Dev Disord. 1992 Dec;22(4):583–600. [PubMed]
  • Bryson SE, Smith IM, Eastwood D. Obstetrical suboptimality in autistic children. J Am Acad Child Adolesc Psychiatry. 1988 Jul;27(4):418–422. [PubMed]
  • Ehlers S, Gillberg C. The epidemiology of Asperger syndrome. A total population study. J Child Psychol Psychiatry. 1993 Nov;34(8):1327–1350. [PubMed]
  • MacKinnon DF, Jamison KR, DePaulo JR. Genetics of manic depressive illness. Annu Rev Neurosci. 1997;20:355–373. [PubMed]
  • Murphy KC, Cardno AG, McGuffin P. The molecular genetics of schizophrenia. J Mol Neurosci. 1996 Summer;7(2):147–157. [PubMed]
  • Smalley SL, Collins F. Brief report: genetic, prenatal, and immunologic factors. J Autism Dev Disord. 1996 Apr;26(2):195–198. [PubMed]
  • Bolton P, Macdonald H, Pickles A, Rios P, Goode S, Crowson M, Bailey A, Rutter M. A case-control family history study of autism. J Child Psychol Psychiatry. 1994 Jul;35(5):877–900. [PubMed]
  • DeLong GR, Dwyer JT. Correlation of family history with specific autistic subgroups: Asperger's syndrome and bipolar affective disease. J Autism Dev Disord. 1988 Dec;18(4):593–600. [PubMed]
  • Gillberg C, Gillberg IC, Steffenburg S. Siblings and parents of children with autism: a controlled population-based study. Dev Med Child Neurol. 1992 May;34(5):389–398. [PubMed]
  • Szatmari P, Jones MB, Tuff L, Bartolucci G, Fisman S, Mahoney W. Lack of cognitive impairment in first-degree relatives of children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry. 1993 Nov;32(6):1264–1273. [PubMed]
  • Jorde LB, Hasstedt SJ, Ritvo ER, Mason-Brothers A, Freeman BJ, Pingree C, McMahon WM, Petersen B, Jenson WR, Mo A. Complex segregation analysis of autism. Am J Hum Genet. 1991 Nov;49(5):932–938. [PubMed]
  • Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH, Rutter M. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am J Hum Genet. 1995 Sep;57(3):717–726. [PubMed]
  • Szatmari P, Jones MB, Fisman S, Tuff L, Bartolucci G, Mahoney WJ, Bryson SE. Parents and collateral relatives of children with pervasive developmental disorders: a family history study. Am J Med Genet. 1995 Aug 14;60(4):282–289. [PubMed]
  • Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405–416. [PubMed]
  • Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995 Jan;25(1):63–77. [PubMed]
  • Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM. Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry. 1985 Jan;142(1):74–77. [PubMed]
  • Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996 Sep 13;273(5281):1516–1517. [PubMed]
  • Schaid DJ, Sommer SS. Genotype relative risks: methods for design and analysis of candidate-gene association studies. Am J Hum Genet. 1993 Nov;53(5):1114–1126. [PubMed]
  • Risch N. Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol. 1990;7(1):3–45. [PubMed]
  • Rutter M, Bailey A, Bolton P, Le Couteur A. Autism and known medical conditions: myth and substance. J Child Psychol Psychiatry. 1994 Feb;35(2):311–322. [PubMed]
  • Tsai LY, Beisler JM. The development of sex differences in infantile autism. Br J Psychiatry. 1983 Apr;142:373–378. [PubMed]
  • Lord C, Schopler E. Differences in sex ratios in autism as a function of measured intelligence. J Autism Dev Disord. 1985 Jun;15(2):185–193. [PubMed]
  • Volkmar FR, Szatmari P, Sparrow SS. Sex differences in pervasive developmental disorders. J Autism Dev Disord. 1993 Dec;23(4):579–591. [PubMed]
  • McLennan JD, Lord C, Schopler E. Sex differences in higher functioning people with autism. J Autism Dev Disord. 1993 Jun;23(2):217–227. [PubMed]
  • Narod SA, Ford D, Devilee P, Barkardottir RB, Lynch HT, Smith SA, Ponder BA, Weber BL, Garber JE, Birch JM, et al. An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995 Jan;56(1):254–264. [PubMed]
  • St George-Hyslop PH, Haines JL, Farrer LA, Polinsky R, Van Broeckhoven C, Goate A, McLachlan DR, Orr H, Bruni AC, Sorbi S, et al. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature. 1990 Sep 13;347(6289):194–197. [PubMed]
  • Spiker D, Lotspeich L, Kraemer HC, Hallmayer J, McMahon W, Petersen PB, Nicholas P, Pingree C, Wiese-Slater S, Chiotti C, et al. Genetics of autism: characteristics of affected and unaffected children from 37 multiplex families. Am J Med Genet. 1994 Mar 15;54(1):27–35. [PubMed]
  • Le Couteur A, Bailey A, Goode S, Pickles A, Robertson S, Gottesman I, Rutter M. A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry. 1996 Oct;37(7):785–801. [PubMed]
  • Ritvo ER, Jorde LB, Mason-Brothers A, Freeman BJ, Pingree C, Jones MB, McMahon WM, Petersen PB, Jenson WR, Mo A. The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. Am J Psychiatry. 1989 Aug;146(8):1032–1036. [PubMed]
  • Piven J, Palmer P, Jacobi D, Childress D, Arndt S. Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. Am J Psychiatry. 1997 Feb;154(2):185–190. [PubMed]
  • Cook EH, Jr, Courchesne R, Lord C, Cox NJ, Yan S, Lincoln A, Haas R, Courchesne E, Leventhal BL. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry. 1997 May;2(3):247–250. [PubMed]
  • Klauck SM, Poustka F, Benner A, Lesch KP, Poustka A. Serotonin transporter (5-HTT) gene variants associated with autism? Hum Mol Genet. 1997 Dec;6(13):2233–2238. [PubMed]

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