Externalizing Behavior: Genetics x Prenatal Nicotine

外化行为：遗传学 x 产前尼古丁

• 批准号: 6757004
• 负责人: Valerie S Knopik
• 金额: $ 3.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757004
• 关键词: alcoholism /alcohol abuse; attention deficit disorder; behavioral /social science research tag; behavioral genetics; child behavior disorders; clinical research; cognition disorders; conduct disorder; disease /disorder etiology; embryo /fetus toxicology; gene environment interaction; genetic susceptibility; genotype; human data; human subject; learning disorders; maternal behavior; nicotine; oppositional defiant disorder; statistics /biometry

DESCRIPTION (provided by applicant): Dr. Valerie Knopik, a behavior geneticist with expertise in quantitative genetics, holds a faculty position in the Department of Psychiatry at Washington University School of Medicine. A Mentored Research Scientist Development Award (K01) is solicited, to support 5 years of research on the joint effects of prenatal nicotine exposure and genetic risk factors in the etiology of externalizing behaviors in children. If granted, this award will allow Dr. Knopik a period of intensive training in molecular genetics, behavioral and physiological effects of nicotine, maternal and child psychopathology assessments, and epidemiology, which will include coursework, laboratory work, clinical exposure, and research under the sponsorship of Dr. Andrew Heath, a renowned behavioral geneticist, and Dr. Richard Todd, a renowned child psychiatrist with expertise in molecular genetics. In addition to the evidence for genetic effects on ADHD (Attention-Deficit Hyperactivity Disorder) and conduct problems, there is suggestive evidence for a role of maternal smoking during pregnancy in the risk of offspring externalizing behaviors. To develop a more comprehensive model for the etiology of externalizing behavior, one must consider the joint effects of genotype and prenatal environment. The overall goal of the research plan is to assess genotype and prenatal nicotine effects on childhood externalizing behaviors using a combination of secondary data analyses and new pilot data collection. Most studies that have focused on prenatal exposure to nicotine have implemented statistical control for other potential risk factors, but since the range of potential confounding factors is unknown, such between-mother controls are likely to be imperfect. Using an innovative within-mother comparison that focuses on externalizing disorder outcomes in offspring of mothers discordant for smoking during pregnancy (i.e., full sibling pairs discordant for prenatal nicotine exposure), the new pilot data collection can overcome many of the limitations of previous research. Dr. Knopik's long-term goal is to become an independent investigator with a program of research on prenatal substance exposure and its role in the etiology of externalizing behavior and associated learning and cognitive deficits, and to identify genes (both maternal and offspring) that may affect childhood outcomes of maternal substance use during pregnancy.

描述（由申请人提供）： Valerie Knopik 博士是一位行为遗传学家，具有定量遗传学方面的专业知识，在华盛顿大学医学院精神病学系担任教职。征集指导研究科学家发展奖（K01），以支持为期 5 年的研究，研究产前尼古丁暴露和遗传风险因素对儿童外化行为病因学的联合影响。如果获得该奖项，诺皮克博士将能够在分子遗传学、尼古丁的行为和生理影响、孕产妇和儿童精神病理学评估以及流行病学方面接受一段时间的强化培训，其中包括课程作业、实验室工作、临床暴露和研究著名行为遗传学家安德鲁·希思博士和具有分子遗传学专业知识的著名儿童精神病学家理查德·托德博士的赞助。除了遗传因素对注意力缺陷多动症（ADHD）和品行问题有影响的证据之外，还有暗示性证据表明，母亲在怀孕期间吸烟会增加后代外化行为的风险。为了建立一种更全面的外化行为病因学模型，必须考虑基因型和产前环境的共同影响。该研究计划的总体目标是结合二手数据分析和新的试点数据收集，评估基因型和产前尼古丁对儿童外化行为的影响。大多数关注产前接触尼古丁的研究都对其他潜在危险因素实施了统计控制，但由于潜在混杂因素的范围尚不清楚，因此母亲之间的这种控制可能并不完善。使用创新的母亲内部比较，重点关注怀孕期间吸烟不一致的母亲（即产前尼古丁暴露不一致的全兄弟姐妹）的后代的疾病结果，新的试点数据收集可以克服以前研究的许多局限性。 Knopik 博士的长期目标是成为一名独立研究者，负责研究产前物质暴露及其在外化行为和相关学习和认知缺陷的病因学中的作用，并确定可能影响产前物质暴露的基因（母亲和后代）。怀孕期间母亲使用药物会影响儿童结局。