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Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills

Molecular Psychiatry volume 11, pages 488–494 (2006)Cite this article

Abstract

We examined three microsatellites in the arginine vasopressin 1a receptor gene (AVPR1a), two in the promoter region (RS1 and RS3) and an intronic microsatellite (AVR), for association with autism as well as scores on the Vineland Adaptive Behavior Scale (VABS), the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Scale-Generic (ADOS-G), measures that are widely used to diagnose autism spectrum disorders. We tested for association between the AVPR1a microsatellites and autism in 116 families (128 probands diagnosed with the ADI-R and ADOS-G using a family-based association test (UNPHASED)). Testing each individual microsatellite showed significant transmission disequilibrium in these families with the AVR intronic microsatellite (UNPHASED: LRS=11.46, global P-value=0.009, df=3). Haplotype analysis of three microsatellites also showed significant association (LRS=144.94, df=103, global P=0.004). Additionally, significant association is observed between these three microsatellite haplotypes and the VABS scores (P=0.009), with the ADI-R (P=0.009) and the ADOS-G (P=0.0000765) diagnoses of autistic disorder versus pervasive developmental disorder-not otherwise specified (PDD-NOS) that were available for 47 of these probands. This is the third consecutive report of an association between the AVPR1a gene and autism spectrum disorders and in the current study a third microsatellite is shown to be associated with autism spectrum disorders as well as haplotypes consisting of all three markers. Importantly, the association appears to be mainly mediated by the role of the AVPR1a gene in shaping socialization skills, similar to its role in lower vertebrates.

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References

  1. Veenstra-Vanderweele J, Christian SL, Cook Jr EH . Autism as a paradigmatic complex genetic disorder. Annu Rev Genomics Hum Genet 2004; 5: 379–405.

    Article  CAS  Google Scholar 

  2. Insel TR, Young LJ . The neurobiology of attachment. Nat Rev Neurosci 2001; 2: 129–136.

    Article  CAS  Google Scholar 

  3. Hammock EA, Young LJ . Variation in the vasopressin V1a receptor promoter and expression: implications for inter- and intraspecific variation in social behaviour. Eur J Neurosci 2002; 16: 399–402.

    Article  Google Scholar 

  4. Thibonnier M . Genetics of vasopressin receptors. Curr Hypertens Rep 2004; 6: 21–26.

    Article  Google Scholar 

  5. Thibonnier M, Graves MK, Wagner MS, Chatelain N, Soubrier F, Corvol P et al. Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. J Mol Cell Cardiol 2000; 32: 557–564.

    Article  CAS  Google Scholar 

  6. Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E et al. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 2002; 7: 503–507.

    Article  CAS  Google Scholar 

  7. Wassink TH, Piven J, Vieland VJ, Pietila J, Goedken RJ, Folstein SE et al. Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry 2004; 9: 968–972.

    Article  CAS  Google Scholar 

  8. Bachner-Melman R, Zohar AH, Bacon-Shnoor N, Elizur Y, Nemanov L, Gritsenko I et al. Linkage between vasopressin receptor AVPR1A promoter region microsatellites and measures of social behavior in humans. J Indiv Differ 2005; 26: 2–10.

    Article  Google Scholar 

  9. Lord C, Rutter M, Le Couteur A . Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994; 24: 659–685.

    Article  CAS  Google Scholar 

  10. Lord C, Risi S, Lambrecht L, Cook Jr EH, Leventhal BL, DiLavore PC et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000; 30: 205–223.

    Article  CAS  Google Scholar 

  11. Sparrow SS, Balla DA, Cicchetti D . Vineland Adaptive Behavior Scales, Interview Edition. American Guidance Service: Circle Pines, MN, 1984.

    Google Scholar 

  12. Sparrow SS, Balla DA, Cicchetti DV . Vineland Adaptive Behavior Scales. American Guidance Services: Minneapolis, MN, 1984.

    Google Scholar 

  13. Wechsler D, Psychological Corporation. WISC-II. [kit] Wechsler Intelligence Scale for Children, 1 manual (xv, 294 24 cm.), 1 stimulus booklet, 25 test forms, 2 mazes response booklets, 2 symbol search response booklets, 1 coding scoring template, 1 object assembly layout shield, 1 box picture arrangement cards (14 sets), 1 set of blocks, 6 sets object assembly puzzles Psychological Corporation Harcourt Brace Jovanobvich: San Antonio, TX, 1991.

    Google Scholar 

  14. Kaufman AS, Kaufman NL . Kaufman Assessment Battery for Children (K-ABC). American Guidance Services: Minneapolis, MN, 1983.

    Google Scholar 

  15. Bayley N . Bayley Scales of Infant Development. Harcourt Brace & Company: San Antonio, TX, 1993.

    Google Scholar 

  16. Stutsman R . Manual for the Merrill–Palmer Scale of Mental Tests. Western Psychological Services: Los Angeles, CA, 1948.

    Google Scholar 

  17. Mullen EM . Mullen Scales of Early Learning. Western Psychological Services: Los Angeles, CA, 1997.

    Google Scholar 

  18. Cattell P . The Measurement of Intelligence of Infants and Young Children-Revised. Psychological Croporation: New York, 1960.

    Google Scholar 

  19. Roid GH, Miller LJ, Lieter RG . Leiter International Performance Scale-Revised: Examiners Manual, vol. xiii. Stoelting: Wood Dale, IL, 1997, p 1v (various pagings).

    Google Scholar 

  20. Thorndike RL, Hagen EP, Sattler JM . The Stanford–Binet Intelligence Scale, Fourth Edition: Guide for Administering and Scoring. Riverside Pub. Co.: Chicago, IL, 1986, 192pp.

    Google Scholar 

  21. Kremer I, Bachner-Melman R, Reshef A, Broude L, Nemanov L, Gritsenko I et al. Association of the serotonin transporter gene with smoking behavior. Am J Psychiatry 2005; 162: 924–930.

    Article  Google Scholar 

  22. Bachner-Melman R, Gritsenko I, Nemanov L, Zohar AH, Dina C, Ebstein RP . Dopaminergic polymorphisms associated with self-report measures of human altruism: a fresh phenotype for the dopamine D4 receptor. Mol Psychiatry 2005; 10: 333–335.

    Article  CAS  Google Scholar 

  23. Sham PC, Curtis D . An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet 1995; 59: 323–336.

    Article  CAS  Google Scholar 

  24. Dudbridge F . Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115–121.

    Article  Google Scholar 

  25. Laird NM, Horvath S, Xu X . Implementing a unified approach to family-based tests of association. Genet Epidemiol 2000; 19 (Suppl 1): S36–S42.

    Article  Google Scholar 

  26. Skuse DH, James RS, Bishop DV, Coppin B, Dalton P, Aamodt-Leeper G et al. Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function (see comments). Nature 1997; 387: 705–708.

    Article  CAS  Google Scholar 

  27. Bachner-Melman R, Zohar AH, Elizur Y, Nemanov L, Gritsenko I, Konis D et al. Association between a vasopressin receptor AVPR1A promoter region microsatellite and eating behavior measured by a self-report questionnaire (Eating Attitudes Test) in a family-based study of a nonclinical population. Int J Eat Disord 2004; 36: 451–460.

    Article  Google Scholar 

  28. Story M, Neumark-Sztainer D, French S . Individual and environmental influences on adolescent eating behaviors. J Am Diet Assoc 2002; 102: S40–S51.

    Article  Google Scholar 

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Acknowledgements

This research was partially supported by the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (NY, RPE and LN).

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Authors and Affiliations

  1. Department of Psychology, Hebrew University, Jerusalem, Israel

    N Yirmiya, S Salomon & R P Ebstein

  2. Human Genetics, Hebrew University, Jerusalem, Israel

    C Rosenberg

  3. Department of Child Psychiatry, Hadassah-Hebrew University Medical School, Jerusalem, Israel

    S Levi

  4. School of Social Work, Hebrew University, Jerusalem, Israel

    C Shulman

  5. S Herzog Memorial Hospital, Jerusalem, Israel

    L Nemanov & R P Ebstein

  6. Genetique Maladies Multifactorielles-Institut de Biologie de Lille, Lille, France

    C Dina

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  1. N Yirmiya
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Correspondence to R P Ebstein.

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Yirmiya, N., Rosenberg, C., Levi, S. et al. Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry 11, 488–494 (2006). https://doi.org/10.1038/sj.mp.4001812

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