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No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies.

ABSTRACT: The effort to understand the genetic basis of human sociality has been encouraged by the diversity and heritability of social traits like cooperation. This task has remained elusive largely because most studies of sociality and genetics use sample sizes that are often unable to detect the small effects that single genes may have on complex social behaviors. The lack of robust findings could also be a consequence of a poor characterization of social phenotypes. Here, we explore the latter possibility by testing whether refining measures of cooperative phenotypes can increase the replication of previously reported associations between genetic variants and cooperation in small samples. Unlike most previous studies of sociality and genetics, we characterize cooperative phenotypes based on strategies rather than actions. Measuring strategies help differentiate between similar actions with different underlaying social motivations while controlling for expectations and learning. In an admixed Latino sample (n = 188), we tested whether cooperative strategies were associated with three genetic variants thought to influence sociality in humans-MAOA-uVNTR, OXTR rs53576, and AVPR1 RS3. We found no association between cooperative strategies and any of the candidate genetic variants. Since we were unable to replicate previous observations our results suggest that refining measurements of cooperative phenotypes as strategies is not enough to overcome the inherent statistical power problem of candidate gene studies.

SUBMITTER: Rivera-Hechem MI

PROVIDER: S-EPMC7757875 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies.

Rivera-Hechem María I MI Rodríguez-Sickert Carlos C Guzmán Ricardo A RA Ramírez-Parada Tadeo T Benavides Felipe F Landaeta-Torres Víctor V Aspé-Sánchez Mauricio M Repetto Gabriela M GM

PloS one 20201223 12

The effort to understand the genetic basis of human sociality has been encouraged by the diversity and heritability of social traits like cooperation. This task has remained elusive largely because most studies of sociality and genetics use sample sizes that are often unable to detect the small effects that single genes may have on complex social behaviors. The lack of robust findings could also be a consequence of a poor characterization of social phenotypes. Here, we explore the latter possibi ...[more]

PMID: 33362272

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Project description:Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes. Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations. Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 (p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p = 0.013) and Insistence on Sameness (p = 0.039). Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction for multiple comparisons was performed for SNPs tested in each gene region, only AVPR1B SNPs remained significantly associated with ASD diagnosis. Conclusions: Autism is a heterogeneous disorder with many genes and pathways that contribute to its development. SNPs and microsatellites in the receptor genes of OT and AVP are associated with ASD diagnosis and measures of social behavior as well as restricted repetitive behaviors. We reported a novel association with ASD and AVPR1B SNPs. Understanding of genotype-phenotype relationships may be helpful in the development of pharmacological interventions for the OT/AVP system.

Dataset Information

No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies.

Publications

No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies.

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