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）：过量饮酒是美国可预防死亡和残疾的重要原因，经济成本巨大。酒精疾病是综合传播的，四分之一的儿童暴露于父母饮酒，与人身健康问题有关，这些问题一直持续到成年。预防计划是针对育儿和家庭环境的，因为它们在早期饮酒和饮酒风险中发挥了理论作用。 "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.不这样做的可能会误解育儿效应，并错误地识别最佳内容和受众的干预措施。使用候选基因的小文献已将育儿作为遗传风险的主持人。但是，由于候选基因通常仅解释结果中的少量差异，因此这些研究通常会提供弱​​，不足的基因环境相关性测试。该R21通过创建两个多基因风险评分来提供对基因环境相关性的更强检验，从而引入了这种问题的新方法。基于理论和研究，我们创建了多基因风险评分，以反映多巴胺能，谷氨酸能，GABA能和胆碱能毒素系统中候选基因的SNP所控制的行为基因组风险。我们使用此分数来测试育儿/家庭环境作为调解人，并且是控制行为基因组风险的主持人。然后，我们添加了“经验衍生的”多基因风险评分，作为基因环境相关性的附加度量，解释了育儿的实质性差异。该分数由SNP组成，SNP与我们与育儿进行的关联分析非常重要，> 1200个SNP（与成瘾有关，但与控制的行为无关，而不包括在“理论驱动”的综合中）。将这种“经验得出的”分数纳入额外的基因环境相关措施，对育儿和家庭环境进行了更严格的测试，作为理论驱动的推定基因组风险对控制行为的影响的介体和主持人。项目目标将通过对三代，纵向，遗传信息的二级数据分析来实现，研究酒精疾病风险的代际传播。 分析将进行两代后代，以提供内部复制。结果将有助于阐明育儿和家庭环境在饮酒结果中的作用， 建议针对家庭预防计划的方向，并为未来的基因环境相互作用提供了一种在饮酒风险发展中的方法。