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Genetics. 2017 Aug;206(4):1969-1984. doi: 10.1534/genetics.117.200642. Epub 2017 May 26.

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior.

Rohde PD1,2,3, Gaertner B4,5,6, Ward K4,5,6, Sørensen P7, Mackay TFC4,5,6.

Author information

1
Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, 8830 Tjele, Denmark palle.d.rohde@mbg.au.dk.
2
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8000 Aarhus, Denmark.
3
ISEQ, Center for Integrative Sequencing, Aarhus University, 8000 Aarhus, Denmark.
4
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695.
5
Program in Genetics, North Carolina State University, Raleigh, North Carolina 27695.
6
W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695.
7
Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, 8830 Tjele, Denmark.

Abstract

Human psychiatric disorders such as schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder often include adverse behaviors including increased aggressiveness. Individuals with psychiatric disorders often exhibit social withdrawal, which can further increase the probability of conducting a violent act. Here, we used the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP) to investigate the genetic basis of variation in male aggressive behavior for flies reared in a socialized and socially isolated environment. We identified genetic variation for aggressive behavior, as well as significant genotype-by-social environmental interaction (GSEI); i.e., variation among DGRP genotypes in the degree to which social isolation affected aggression. We performed genome-wide association (GWA) analyses to identify genetic variants associated with aggression within each environment. We used genomic prediction to partition genetic variants into gene ontology (GO) terms and constituent genes, and identified GO terms and genes with high prediction accuracies in both social environments and for GSEI. The top predictive GO terms significantly increased the proportion of variance explained, compared to prediction models based on all segregating variants. We performed genomic prediction across environments, and identified genes in common between the social environments that turned out to be enriched for genome-wide associated variants. A large proportion of the associated genes have previously been associated with aggressive behavior in Drosophila and mice. Further, many of these genes have human orthologs that have been associated with neurological disorders, indicating partially shared genetic mechanisms underlying aggression in animal models and human psychiatric disorders.

KEYWORDS:

Drosophila melanogaster; GBLUP; GFBLUP; GenPred; Genomic Selection; Shared data resource; social experience; social isolation

PMID:
28550016
PMCID:
PMC5560801
DOI:
10.1534/genetics.117.200642
[Indexed for MEDLINE]
Free PMC Article

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