Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat

Abstract

In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of alleles in 798 outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2 fold heritability enrichment. To confirm these findings on coping behavior, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviorally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our study is the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence coping and impulsive behavior, and suggest these effects might be significant in other mammals, including humans.

Keywords: MPP; MultiParental Populations; Multiparent Advanced Generation Inter-Cross (MAGIC).

Figure 1

Frequency distributions of the off-diagonal elements of the Genetic Relationship Matrices $K_{+}$ (A) and $K_{-}$ (B) in HS rats. In each plot, the distributions of siblings (black) and non-siblings (red) are shown separately; x-axis shows the number of shared alleles, y-axis is the smoothed density.

Figure 2

(A) Heritability of 199 traits partitioned into components $h_{+}^2$ (y-axis) and $h_{-}^2$ (x-axis) associated respectively with PoE and non-PoE. Each dot represents one trait. Coping-Style traits are in green, other behavioral traits are in red. (B) Heritability partitioned into maternal and paternal components, color-coded as in (A).

Figure 3

Box-and-whisker plots showing parent-of-origin effects on three behaviors (A-C) and gender effects on Stretch Attendance Posture (D), in 68 F1 rats from a reciprocal cross between strains RHA and RLA. x-axis indicates direction of reciprocal cross (fRHA/mRLA vs. fRLA/mRHA) in A-C and sex (M:Male, F:Female) in D. y-axis is behavioral phenotype score (A: Time in Open Section/s, B: number of Entries into Open Section, C: Latency to enter into an open section/s, in Elevated Zero Maze, D: Number of stretch attendance postures (SAP) in Elevated Zero Maze). Thick black horizontal line indicates median, gray box indicates range of central 50% of data points, and outer whiskers the 90% range.