Mapping genotype-expression associations in Heterogeneous Stock rat brains to advance behavioral genetics research [Nucleus accumbens core]

Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.针对冲动性与奖赏驱动行为的遗传影响研究，高度依赖远交群动物种群，包括同源远交系（Heterogeneous Stock, HS）大鼠，以获取鉴定基因型-性状关联所需的遗传多样性。此类关联虽已被大量检出，但往往难以明确所鉴定基因组区域附近的具体基因或其他遗传元件，究竟是该关联的功能性调控因素。由于此类性状部分由基因表达介导，因此在该类动物中绘制基因型与基因表达间的关联图谱，将有助于发现此类性状关联并深化对其的理解。为此，我们从88只HS大鼠中获取了5个脑区的基因型与RNA测序（RNA-Seq）基因表达数据，并为每个脑区绘制了表达数量性状基因座（expression quantitative trait loci, eQTLs）图谱。我们在每个脑区的逾3000个基因中鉴定出顺式表达数量性状基因座（cis-eQTLs），并通过等位基因特异性表达验证了其效应量。本研究数据集将助力复杂行为性状遗传影响相关的全新发现。