Exploring a novel approach to clarify parenting effects on drinking outcomes

探索一种新方法来阐明育儿对饮酒结果的影响

• 批准号: 8733114
• 负责人: LAURIE A CHASSIN
• 金额: $ 16.92万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733114
• 关键词: Accounting; Adolescence; Adolescent; Adult; Age; Alcohol abuse; Alcohols; Behavioral; Candidate Disease Gene; Cessation of life; Child; Data; Data Analyses; Development; Discipline; Disease; Disease susceptibility; Environment; Esthesia; Family; Future; Generations; Genes; Genetic Risk; Genomics; Glutamates; Goals; Heavy Drinking; Impulsivity; Intervention; Literature; Long-Term Effects; Longitudinal Studies; Measures; Mediating; Mediator of activation protein; Mental Health; Methods; Modeling; Monitor; Muscarinics; Outcome; Outcome Study; Parenting behavior; Parents; Prevention; Prevention program; Public Health; Research; Risk; Role; Stress; Symptoms; System; Testing; addiction; alcohol research; alcohol risk; base; children of alcoholics; cholinergic; disability; drinking; early drinking; economic cost; gene environment interaction; high risk; improved; innovation; intergenerational; novel strategies; offspring; parental role; physical conditioning; premature; problem drinker; prospective; public health relevance; research study; theories; transmission process; underage drinking

DESCRIPTION (provided by applicant): Excessive drinking is an important cause of preventable death and disability in the U.S., with large economic costs. Alcohol disorders are transmitted intergenerationally, and one in four U.S. children is exposed to parent problem drinking, with associated mental and physical health problems that persist into adulthood. Prevention programs have targeted parenting and family environment because of their theoretical roles in early drinking and risk for alcohol disorder. "Deviance proneness" theories posit that alcoholic parents provide disorganized and conflictual family environments and parenting that lacks support, monitoring, and consistent discipline, which, in turn exacerbate the effects of a genetically-transmitted vulnerability to "behavioral under control" on alcohol outcomes However, studies are needed to clarify the role of parenting/family environment in the context of correlated genetic risk. Failing to do so risks mis-estimating parenting effects and mis-identifying the optimal content and audiences for intervention. A small literature using candidate genes has tested parenting as a moderator of genetic risk. However, because candidate genes typically explain only small amounts of variance in outcomes, these studies often provide weak, insufficient tests of gene-environment correlation. This R21 introduces a novel approach to this problem by creating two polygenic risk scores to provide a stronger test of gene-environment correlation. Based on theory and research, we create a polygenic risk score to reflect presumed genomic risk for behavioral under control with SNPs from candidate genes in dopaminergic, glutamatergic, GABAergic, and cholinergic muscarinic systems. We use this score to test parenting/family environment as a mediator and a moderator of presumed genomic risk for behavioral under control. We then add an "empirically-derived" polygenic risk score as an additional measure of gene-environment correlation that explains substantial variance in parenting. This score is composed of SNPs that are significant in association analyses that we conduct with parenting and >1,200 SNPs (relevant to addiction but not specific to behavioral under control and not included in the "theory-driven" composite). Incorporating this "empirically- derived" score as an additional gene-environment correlation measure, provides a more rigorous test of parenting and family environment as mediators and moderators of the effects of theory-driven presumed genomic risk for behavioral under control. The project goals will be accomplished through secondary data analysis of a three-generation, longitudinal, genetically informative, study of the intergenerational transmission of risk for alcohol disorders. Analyses will be conducted for two generations of offspring to provide an internal replication. The results will help to clarify the role of parenting and family environment in drinking outcomes, suggest directions for family-based prevention programs, and provide a method for future studies of gene- environment interplay in the development of risk for alcohol disorder.

描述（由申请人提供）：过度饮酒是美国可预防的死亡和残疾的一个重要原因，造成巨大的经济损失。酒精障碍会代际传播，四分之一的美国儿童受到父母酗酒的影响，相关的心理和身体健康问题一直持续到成年。预防计划以养育和家庭环境为目标，因为它们在早期饮酒和酒精障碍风险中发挥着理论上的作用。 “偏差倾向”理论认为，酗酒的父母提供了无组织和冲突的家庭环境，以及缺乏支持、监控和一致纪律的养育方式，这反过来又加剧了遗传性易受“控制行为”影响的酒精结果的影响。然而，需要研究来阐明养育/家庭环境在相关遗传风险背景下的作用。如果不这样做，可能会错误地估计育儿效果，并错误地识别干预的最佳内容和受众。一份使用候选基因的小型文献测试了养育方式作为遗传风险调节因素的作用。然而，由于候选基因通常只能解释结果中的少量差异，因此这些研究通常对基因-环境相关性提供的测试薄弱且不充分。 R21 通过创建两个多基因风险评分来解决这个问题，以提供更强的基因-环境相关性测试。基于理论和研究，我们创建了一个多基因风险评分，以反映多巴胺能、谷氨酸能、GABA 能和胆碱能毒蕈碱系统中候选基因的 SNP 控制下的行为的假定基因组风险。我们使用这个分数来测试养育/家庭环境作为控制行为的假定基因组风险的中介和调节因素。然后，我们添加“经验得出的”多基因风险评分作为基因-环境相关性的额外衡量标准，解释了养育方式的巨大差异。该分数由在我们与育儿进行的关联分析中具有重要意义的 SNP 和 >1,200 个 SNP（与成瘾相关，但不特定于受控制的行为且不包含在“理论驱动”组合中）组成。将这种“经验派生”分数作为额外的基因-环境相关性测量，提供了对养育和家庭环境的更严格的测试，作为理论驱动的假定基因组风险对受控行为的影响的中介者和调节者。该项目的目标将通过对酒精障碍风险代际传播的三代、纵向、遗传信息研究的二次数据分析来实现。 将对两代后代进行分析以提供内部复制。研究结果将有助于阐明养育方式和家庭环境在饮酒结果中的作用， 为基于家庭的预防计划提出方向，并为未来研究酒精障碍风险发展中的基因-环境相互作用提供方法。