Elsevier

Biological Psychiatry

Volume 63, Issue 10, 15 May 2008, Pages 911-916
Biological Psychiatry

Archival Report
Genes Controlling Affiliative Behavior as Candidate Genes for Autism

https://doi.org/10.1016/j.biopsych.2007.11.015Get rights and content

Background

Autism spectrum disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors.

Methods

On the basis of the existing literature, in this study we examined the hypothesis of allelic associations between genetic variants in six genes involved in control of maternal and affiliative behaviors (OXT, OXTR, PRL, PRLR, DβH, and FOSB). One hundred and seventy-seven probands with ASD from 151 families (n = 527) were assessed with a set of related instruments capturing multiple facets of ASD. Multivariate and univariate phenotypes were constructed from these assessments and subjected to genetic linkage and association analyses with PBAT and FBAT software.

Results

The resulting pattern of findings, in general, confirmed the hypotheses of the significance of the genes involved in the development of affiliative behaviors in the manifestation of ASD (p values ranging from .000005 to .05); statistically speaking, the strongest results were obtained for allelic associations with the PRL, PRLR, and OXTR genes.

Conclusions

These preliminary data provide additional support for the hypothesis that the allelic variants of genes necessary for the development of species-typical affiliative behaviors are associated with ASD. Independent replication of these findings is needed and studies of other genes associated with affiliative behaviors are indicated.

Section snippets

Participants

To test our hypotheses on the relevance of one or more of six genes involved in control of affiliative behaviors (OXT, OXTR, PRL, PRLR, DβH, and FOSB) to ASD, we genotyped DNA from a sample of probands with autism and their families available through the Yale Child Study Center. The sample consisted of 527 participants (322 male, and 205 female), of which 177 were classified as probands (Table 1). These participants formed 151 nuclear families. Forty-one percent of the families had only one

Results

The patterns of analysis for multivariate and univariate phenotypes are quite consistent. Specifically, for multivariate analyses, the lowest p values obtained were those for PRLR (p = .000005, with the multivariate indicator of Communication Skills and rs7727306; and p = .000249, with the multivariate ADI phenotype, ADI Group and rs35614689) and PRL (p = .000085 and p = .006957, with the multivariate ADI phenotype and rs1341239 and rs1205961, respectively). The pattern of univariate results is

Discussion

A number of observations are of interest here.

First, the evidence of the involvement of the prolactin system at the genetic level is novel, although based on evidence in the literature. It is of interest and importance that both the PRL ligand and the receptor show allelic associations with ASD. This might suggest the involvement of the PRL pathway as a whole and possibly of other pathways with which PRL interacts. For example, there is evidence that stimulation by PRL of mouse mammary glands

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