The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the “Positive Valence Systems” domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of “effort” and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6–12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses “effort” according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of hard-task choice and a separate genetic locus associated with reward sensitivity. Gene-set enrichment analysis yielded significant associations between “effort” and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish “effort” as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.

中文翻译：

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儿童和成人努力评估和精神病理学的新全基因组关联

研究领域标准 (RDoC) 计划由美国国家心理健康研究所建立，作为一个多层次、与疾病无关的框架，用于通过指定领域和结构（包括专注于奖励相关的“正价系统”领域）分析人类精神病理学行为。本研究调查了 1215 名 6-12 岁儿童及其父母 ( n = 1044)的“努力”的奖励评估子结构及其与遗传标记、功能神经生物学途径和精神病理学多基因风险评分的关系 。所有参与者都完成了奖励任务的努力支出（EEfRT），该任务根据两个定量指标评估“努力”：困难任务选择和奖励敏感性。在MAGMA中进行遗传关联分析，利用 EEfRT 结果变量作为全基因组关联研究表型来计算 SNP 和基因水平关联。全基因组关联分析发现两个不同的基因位点与困难任务选择的测量显着相关，以及一个与奖励敏感性相关的单独的基因位点。基因集富集分析发现“努力”与涉及奖励处理相关途径的多个基因集之间存在显着关联，包括多巴胺受体信号传导、边缘系统和前脑发育以及对可卡因的生物反应。这些结果有助于将“努力”确立为在基因水平上理解奖励相关行为的相关结构，并支持用于评估与疾病无关的精神病理学的 RDoC 框架。