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      No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences

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          Abstract

          Background

          Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare.

          Methodology/Principal Findings

          We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games.

          Conclusion

          We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant.

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          Most cited references 14

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          Oxytocin, vasopressin, and the neurogenetics of sociality.

           Z Donaldson,  L Young (2008)
          There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.
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            Common genetic variants on 5p14.1 associate with autism spectrum disorders.

            Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
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              Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice.

              The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr(-/-)) and compared them with OXT-deficient (Oxt(-/-)) mice. Oxtr(-/-) mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr(-/-) dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr(-/-) males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr(-/-) males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt(-/-) males from Oxt(-/-) dams, but not from Oxt(+/-) dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                16 June 2010
                : 5
                : 6
                Affiliations
                [1 ]Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, United States of America
                [2 ]Department of Human Evolutionary Biology, Harvard University, Boston, Massachusetts, United States of America
                [3 ]Department of Economics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
                [4 ]Department of Economics, Stockholm School of Economics, Stockholm, Sweden
                [5 ]Department of Political Science, University of California San Diego, La Jolla, California, United States of America
                [6 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [7 ]Department of Economics, Harvard University, Boston, Massachusetts, United States of America
                [8 ]Department of Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
                Institute of Evolutionary Biology (CSIC-UPF), Spain
                Author notes

                Conceived and designed the experiments: DAC MJ PL BW. Performed the experiments: DAC MJ BW. Analyzed the data: CA DAC BW LW. Contributed reagents/materials/analysis tools: LW. Wrote the paper: CA DAC MJ CTD BW JRB LW.

                Article
                10-PONE-RA-17830R1
                10.1371/journal.pone.0011153
                2886839
                20585395
                Apicella et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 8
                Categories
                Research Article
                Evolutionary Biology
                Genetics and Genomics
                Neuroscience

                Uncategorized

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