GxE in Early Childhood: Twin Mothers

描述（由申请人提供）：本R01申请是四个协调的R01基金之一，其主要重点是基因-环境相互作用（GE相关性和GxE相互作用）对幼儿早期社会、情感和行为问题变异的影响的前瞻性表征。本R01使用了双胞胎的孩子（COT）范式，建立在对女性同性双胞胎的前瞻性研究的基础上，这些双胞胎首次在青春期进行评估（N=3277对双胞胎在成年早期进行评估，年龄在18-26岁）。COT设计对于解决(1)与伴侣选择相关的基因相关效应，(2)由于父母的遗传性状预测后代高风险环境暴露的可能性增加而产生的基因相关效应尤其有效。假设检验将整合在一个考虑3个元模型的理论框架内-(行为控制/去抑制；行为抑制/负面影响；药理学损害/物质依赖)，以了解年轻女性之间的遗传和表型差异，以及早期经历（童年创伤、养育环境）的差异，如何对她们现在或未来的后代造成逐步级联的环境风险。从发育的角度考虑基因与环境的相互作用，包括孕前影响（伴侣选择、关系形成）、产前影响（早孕或晚孕、孕期母亲吸烟和饮酒）、产后直接环境（家庭社会经济劣势、高危社区）、早期家庭环境（父母关系和关系破裂、父母行为）；早期创伤事件)和外部环境影响（获得高质量日托和学校教育）。从年轻的成年女性双胞胎中收集两波数据，通过电话访谈（第一波目标N=2622名访谈对象，2年随访N=2490名访谈对象）将描述关系和怀孕史、早期育儿行为、感知伴侣行为和情绪问题（预计N=2100名伴侣，每波20%完成访谈）以及儿童情绪和行为问题（预计N=2000名子女）。并将获得双风险因素的最新评估。结合R01s 2-4，这些数据将有力地解决关于GE对幼儿相互作用的假设。

DESCRIPTION (provided by applicant): This R01 application is one of four coordinated R01 Grants whose primary focus is the prospective characterization of effects on variation in the early social, emotional and behavioral problems of young children of gene-environment interplay (GE correlation and GxE interaction). This R01 makes use of a children-of-twins (COT) paradigm, building upon a prospective study of female like-sex twin pairs who were first assessed in adolescence (N=3277 twins assessed at wave 4 in early adulthood, ages 18-26). The COT design is particularly powerful for resolving (i) GE correlation effects associated with partner selection, (ii) GE correlation effects arising because heritable traits in parents predict increased probability of offspring high risk environmental exposures. Hypothesis-testing will be integrated within a theoretical framework that considers 3 meta-models -(behavioral under-control/disinhibition; behavioral inhibition/negative affect; pharmacologic impairment/substance dependence) for understanding how genetic and phenotypic differences between young women, in combination with differences in early experience (childhood trauma, rearing environment), contribute to risk of a progressive cascade of environmental risk for their present or future offspring. Gene-environment interplay is considered from a developmental perspective that considers pre-conception effects (partner selection, relationship formation), prenatal effects (early versus delayed pregnancy, maternal smoking and drinking during pregnancy), immediate post-natal environment (family socioeconomic disadvantage, high-risk neighborhood), early family environment (parent-parent relationship and relationship dissolution, and parenting behaviors; early traumatic events) and external environmental influences (access to high quality day-care, schooling). Two waves of data collection from the young adult female twin pairs, by telephone interview (target N=2622 interviews at wave one, N=2490 interviews at 2-year follow-up) will characterize relationship and pregnancy histories and early parenting behavior, perceived partner behavioral and emotional problems (projected N=2100 partners, with 20 percent completing interviews at each wave) and children's emotional and behavioral problems (projected N=2000 offspring), and will obtain updated assessments of twin risk-factors. In conjunction with R01s 2-4, these data will permit a powerful resolution of hypotheses concerning GE interplay effects on young children.