Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism
Abstract
Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There have been three independent reports of a genetic association between polymorphisms in the human AVPR1A and symptoms of ASD.
“In addition, there have now been three independent reports of a genetic association between these polymorphisms in the human AVPR1A and symptoms of ASD [47–49].”
From The prairie vole: An emerging model organism for understanding the social brain (2010) · cites this paper as [47]
Cites
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
Self-citationLord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · see citing works
Self-citationPedCheck: A Program for Identification of Genotype Incompatibilities in Linkage Analysis
O'Connell, J. R., & Weeks, D. E. (1998) · The American Journal of Human Genetics · doi:10.1086/301904 · Cited by 2,063 · see citing works
Are Rare Variants Responsible for Susceptibility to Complex Diseases?
Pritchard, J. K. (2001) · The American Journal of Human Genetics · doi:10.1086/321272 · Cited by 1,197 · see citing works
Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function
Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., & Darnell, R. B. (2001) · Cell · doi:10.1016/s0092-8674(01)00566-9 · Cited by 952 · see citing works
Park‐Wyllie, L. Y., Mazzotta, P., Pastuszak, A. L., Moretti, M. E., Béïque, L. C., Hunnisett, L., Friesen, M. H., Jacobson, S., Kasapinovic, S., Chang, D., et al. (2000) · Teratology · doi:10.1002/1096-9926(200012)62:6 · Cited by 939 · see citing works
The TDT and other family-based tests for linkage disequilibrium and association.
(1996) · PubMed Central · Cited by 901 · see citing works
Young, L. J., Nilsen, R., Waymire, K. G., MacGregor, G. R., & Insel, T. R. (1999) · Nature · doi:10.1038/23475 · Cited by 488 · see citing works
Evidence of linkage between the serotonin transporter and autistic disorder
Cook, E., Yeung-Courchesne, R., Lord, C., Cox, N. J., Yan, S., Lincoln, A. J., Haas, R., Courchesne, E., & LEVENTHAL, B. L. (1997) · Molecular Psychiatry · doi:10.1038/sj.mp.4000266 · Cited by 426 · see citing works
Self-citationLinkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers
Cook, E. H., Courchesne, R. Y., Cox, N. J., Lord, C., Gonen, D., Guter, S. J., Lincoln, A., Nix, K., Haas, R., Leventhal, B. L., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/301832 · Cited by 369 · see citing works
Self-citationReelin gene alleles and haplotypes as a factor predisposing to autistic disorder
Persico, A. M., D'Agruma, L., Maiorano, N., Totaro, A., Militerni, R., Bravaccio, C., Wassink, T. H., Schneider, C., Melmed, R., Trillo, S., et al. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000850 · Cited by 337 · see citing works
Association between a GABRB3 polymorphism and autism
Buxbaum, J. D., Silverman, J. M., Smith, C. J. W., Greenberg, D. A., Kilifarski, M., Reichert, J. G., Cook, E. H., Fang, Y., Song, C.-Y., & Vitale, R. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001011 · Cited by 322 · see citing works
Neuropeptides and the evolution of social behavior
Insel, T. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00146-x · Cited by 264 · see citing works
Serotonin transporter (5-HTT) gene variants associated with autism?
Klauck, S. M. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.13.2233 · Cited by 261 · see citing works
Evidence supporting WNT2 as an autism susceptibility gene
Wassink, T. H., Piven, J., Vieland, V. J., Huang, J., Swiderski, R. E., Pietila, J., Braun, T. A., Beck, G. E., Folstein, S. E., Haines, J. L., et al. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1401 · Cited by 206 · see citing works
Role of the serotonin transporter gene in the behavioral expression of autism
Tordjman, S., Gutknecht, L., Carlier, M., Spitz, E., Antoine, C., Slama, F., Carsalade, V, Cohen, D. J., Ferrari, P., Roubertoux, P. L., et al. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000873 · Cited by 196 · see citing works
Evidence for an association with the serotonin transporter promoter region polymorphism and autism
Yirmiya, N., Pilowsky, T., Nemanov, L., Arbelle, S., Feinsilver, T., Fried, I., & Ebstein, R. P. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1365 · Cited by 168 · see citing works
Kim, S.-J., Cox, N. J., Yeung-Courchesne, R., Lord, C., Corsello, C. M., Akshoomoff, N., Guter, S. J., LEVENTHAL, B. L., Courchesne, E., & Cook, E. H. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001033 · Cited by 150 · see citing works
Self-citationThibonnier, M., Graves, M. K., Wagner, M., Auzan, C., Clauser, É., & Willard, H. F. (1996) · Genomics · doi:10.1006/geno.1996.0055 · Cited by 80 · see citing works
Thibonnier, M., Graves, M. K., Wagner, M., Chatelain, N., Soubrier, F., Corvol, P. L., Willard, H. F., & Jeunemaı̂tre, X. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1108 · Cited by 73 · see citing works
Neuropsychological effects of vasopressin in healthy humans
Born, J., Pietrowsky, R., & L. Fehm, H. (1999) · Progress in brain research · doi:10.1016/s0079-6123(08)61595-2 · Cited by 42 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768 · see citing works
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688 · see citing works
Oxytocin, vasopressin, and the neurogenetics of sociality
Donaldson, Z. R., & Young, L. J. (2008) · Science · doi:10.1126/science.1158668 · Cited by 1,645 · see citing works
Self-citationThe neurobiology of pair bonding.
Young, L. J., & Wang, Z. (2004) · Nature Neuroscience · doi:10.1038/nn1327 · Cited by 1,523 · see citing works
Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder
Dawson, G. (2008) · Development and Psychopathology · doi:10.1017/s0954579408000370 · Cited by 1,138 · see citing works
Insel, T. R. (2010) · Neuron · doi:10.1016/j.neuron.2010.03.005 · Cited by 1,044 · see citing works
Self-citationOxytocin, vasopressin, and human social behavior
Heinrichs, M., von Dawans, B., & Domes, G. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.005 · Cited by 799 · see citing works
Lim, M. M., Wang, Z., Olazábal, D. E., Ren, X., Terwilliger, E. F., & Young, L. J. (2004) · Nature · doi:10.1038/nature02539 · Cited by 628 · see citing works
Self-citationNeuropeptidergic regulation of affiliative behavior and social bonding in animals
Lim, M. M., & Young, L. J. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.028 · Cited by 624 · see citing works
Self-citationMicrosatellite instability generates diversity in brain and sociobehavioral traits
Hammock, E. A. D., & Young, L. J. (2005) · Science · doi:10.1126/science.1111427 · Cited by 545 · see citing works
Self-citationBielsky, I. F., Hu, S.-B., Szegda, K. L., Westphal, H., & Young, L. J. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300360 · Cited by 531 · see citing works
Self-citationVasopressin: Behavioral roles of an “original” neuropeptide
Caldwell, H. K., Lee, H.-J., Macbeth, A. H., & Young, W. S. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.10.007 · Cited by 504 · see citing works
Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans
HEINRICHS, M., & DOMES, G. (2008) · Progress in brain research · doi:10.1016/s0079-6123(08)00428-7 · Cited by 479 · see citing works
Walum, H., Westberg, L., Henningsson, S., Neiderhiser, J. M., Reiss, D., Igl, W., Ganiban, J. M., Spotts, E. L., Pedersen, N. L., Eriksson, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803081105 · Cited by 460 · see citing works
Sex differences in oxytocin and vasopressin: Implications for autism spectrum disorders?
CARTER, C. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.08.025 · Cited by 432 · see citing works
Vitamin D hormone regulates serotonin synthesis. Part 1: Relevance for autism
Patrick, R. P., & Ames, B. N. (2014) · The FASEB Journal · doi:10.1096/fj.13-246546 · Cited by 414 · see citing works
Autism, oxytocin and interoception
Quattrocki, E., & Friston, K. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.09.012 · Cited by 393 · see citing works
Rilling, J. K., DeMarco, A. C., Hackett, P. D., Chen, X., Gautam, P., Stair, S., Haroon, E., Thompson, R., Ditzen, B., Patel, R., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.022 · Cited by 343 · see citing works
“In addition to ASD, studies have begun to investigate the effectiveness of intranasal OT as a treatment for schizophrenia, social anxiety disorder and depression (Striepens, et al., 2011).”
BackgroundInfluentialFeldman, R., Monakhov, M., Pratt, M., & Ebstein, R. P. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.008 · Cited by 352 · see citing works
Dopaminergic-neuropeptide interactions in the social brain
Skuse, D. H., & Gallagher, L. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2008.09.007 · Cited by 340 · see citing works
A. Bartz, J., & Hollander, E. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.018 · Cited by 311 · see citing works
The contributions of oxytocin and vasopressin pathway genes to human behavior
Ebstein, R. P., Knafo, A., Mankuta, D., Chew, S. H., & Lai, P. S. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.014 · Cited by 283 · see citing works
Israel, S., Lerer, E., Shalev, I., Uzefovsky, F., Riebold, M., Laiba, E., Bachner-Melman, R., Maril, A., Bornstein, G., Knafo, A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005535 · Cited by 278 · see citing works
The prairie vole: An emerging model organism for understanding the social brain
McGraw, L. A., & Young, L. J. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.006 · Cited by 276 · see citing works
Self-citationDAWSON, G., WEBB, S. J., WIJSMAN, E., SCHELLENBERG, G., ESTES, A., MUNSON, J., & FAJA, S. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050327 · Cited by 247 · see citing works
Prenatal programming of postnatal plasticity?
Pluess, M., & Belsky, J. (2011) · Development and Psychopathology · doi:10.1017/s0954579410000623 · Cited by 235 · see citing works
Yirmiya, N., Rosenberg, C., Levi, S., Salomon, S., Shulman, C., Nemanov, L., Dina, C., & Ebstein, R. P. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001812 · Cited by 232 · see citing works
Examination of AVPR1a as an autism susceptibility gene
Wassink, T. H., Piven, J., Vieland, V. J., Pietila, J., Goedken, R. J., Folstein, S. E., & Sheffield, V. C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001503 · Cited by 212 · see citing works
Genetics of human aggressive behaviour
Craig, I. W., & Halton, K. E. (2009) · Human Genetics · doi:10.1007/s00439-009-0695-9 · Cited by 213 · see citing works
Albers, H. E. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.07.001 · Cited by 200 · see citing works
Lukas, M., Bredewold, R., Neumann, I. D., & Veenema, A. H. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.06.020 · Cited by 183 · see citing works
Human neuroimaging of oxytocin and vasopressin in social cognition
Zink, C. F., & Meyer-Lindenberg, A. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.01.016 · Cited by 176 · see citing works
Anatomy and neurochemistry of the pair bond
Young, L. J., Murphy Young, A. Z., & Hammock, E. A. D. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20771 · Cited by 163 · see citing works
Self-citationMiller, M., Bales, K. L., Taylor, S. L., Yoon, J., Hostetler, C. M., Carter, C. S., & Solomon, M. (2013) · Autism Research · doi:10.1002/aur.1270 · Cited by 151 · see citing works
Oxytocin and experimental therapeutics in autism spectrum disorders
BARTZ, J., & HOLLANDER, E. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00435-4 · Cited by 139 · see citing works
Vasopressin innervation of the mouse ( <i>Mus musculus</i> ) brain and spinal cord
Rood, B. D., & De Vries, G. J. (2011) · Journal of Comparative Neurology · doi:10.1002/cne.22635 · Cited by 134 · see citing works
Uzefovsky, F., Shalev, I., Israel, S., Edelman, S., Raz, Y., Mankuta, D., Knafo-Noam, A., & Ebstein, R. P. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2014.11.007 · Cited by 131 · see citing works
Oxytocin, vasopressin, and the motivational forces that drive social behaviors
Caldwell, H. K., & Albers, H. E. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_390 · Cited by 129 · see citing works
Neuropeptides and the social brain: potential rodent models of autism
Lim, M. M., Bielsky, I. F., & Young, L. J. (2005) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.05.006 · Cited by 129 · see citing works
Self-citationNeurobiological correlates of social functioning in autism
Neuhaus, E., Beauchaine, T. P., & Bernier, R. (2010) · Clinical Psychology Review · doi:10.1016/j.cpr.2010.05.007 · Cited by 122 · see citing works
Oxytocin and vasopressin: genetics and behavioral implications
Caldwell, H. K., & Young, W. S. (2006) · Handbook of Neurochemistry and Molecular Neurobiology · doi:10.1007/978-0-387-30381-9_25 · Cited by 113 · see citing works
Impact of prosocial neuropeptides on human brain function
MEYERLINDENBERG, A. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00436-6 · Cited by 109 · see citing works
Barrett, C. E., Keebaugh, A. C., Ahern, T. H., Bass, C. E., Terwilliger, E. F., & Young, L. J. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.01.005 · Cited by 100 · see citing works
Self-citationTabak, B. A., Meyer, M. L., Castle, E., Dutcher, J. M., Irwin, M. R., Han, J. H., Lieberman, M. D., & Eisenberger, N. I. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.006 · Cited by 67 · see citing works
Levin, R., Heresco-Levy, U., Bachner-Melman, R., Israel, S., Shalev, I., & Ebstein, R. P. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.12.014 · Cited by 68 · see citing works
Caldwell, H. K. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-1704-0_12 · Cited by 58 · see citing works
On switches and knobs, microsatellites and monogamy
Young, L. J., & Hammock, E. A. D. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.02.010 · Cited by 58 · see citing works
Self-citationDonaldson, Z. R., & Young, L. J. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003729 · Cited by 52 · see citing works
Lee, R. J., Coccaro, E. F., Cremers, H., McCarron, R., Lu, S.-F., Brownstein, M. J., & Simon, N. G. (2013) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2013.00100 · Cited by 50 · see citing works
Brain vasopressin signaling modulates aspects of maternal behavior in lactating rats
Bayerl, D. S., & Bosch, O. J. (2019) · Genes, Brain and Behavior · doi:10.1111/gbb.12517 · Cited by 46 · see citing works
Yang, S. Y., Cho, S.-C., Yoo, H. J., Cho, I. H., Park, M., Kim, B.-N., Kim, J.-W., Shin, M.-S., Park, T.-W., Son, J.-W., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.05.050 · Cited by 45 · see citing works
Self-citationThe sociability spectrum: evidence from reciprocal genetic copy number variations
López-Tobón, A., Trattaro, S., & Testa, G. (2020) · Molecular Autism · doi:10.1186/s13229-020-00347-0 · Cited by 20 · see citing works
Vollebregt, O., Koyama, E., Zai, C. C., Shaikh, S. A., Lisoway, A. J., Kennedy, J. L., & Beitchman, J. H. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.05.062 · Cited by 13 · see citing works
Kirsch, P., & Meyer-Lindenberg, A. (2010) · The Neurochemical Basis of Autism · doi:10.1007/978-1-4419-1272-5_10 · Cited by 6 · see citing works
- Authors
- Kim, S.-J., Young, L. J., Gonen, D., Veenstra-VanderWeele, J., Courchesne, R., Courchesne, E., Lord, C., Leventhal, B. L., Cook Jr, E. H., & Insel, T. R.
- Affiliations
- University of Chicago (US)
- Emory University (US)
- University of California San Diego (US)
- Venue
- Molecular Psychiatry
- Published
- 2002-06-01
- Volume
- 7
- Issue
- 5
- Pages
- 503-507
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2059731224
- Cited by
- 265
- References
- 21
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 5 · 2021: 10 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 8 · 2015: 11 · 2014: 23 · 2013: 14 · 2012: 18
- FWCI
- 18.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh001389-03, 5r01mh052223-05)
- National Institute of Mental Health (R01 MH52223, K02MH01389, R01MH056538)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD035482)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, vasopressin, AVPR1A, V1a receptor, 5'-flanking region, microsatellite polymorphism, single nucleotide polymorphisms, transmission disequilibrium, social behavior, social reciprocity, genetic susceptibility
- MeSH terms
- Autistic Disorder, Base Sequence, Exons, Humans, Polymorphism, Genetic, Promoter Regions, Genetic, Social Behavior, Linkage Disequilibrium, Receptors, Vasopressin, Codon, Initiator, Codon, Terminator, Microsatellite Repeats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
