? The goal of our proposed study is to elucidate cause-and-effect relationships and mechanisms that link short sleep duration (SSD) and overweight or obesity (OWO) in children, adolescents, and young adults using a large existent prospective twin cohort. We enrolled about 2,000 twin pairs in 1998-2000 in Anqing, China, when the twins were 6-21 years of age. This twin cohort is being followed (1st F/U) by a NICHD funded study (R01HD049059) to identify precursors of metabolic syndrome (MS). The second follow-up (2nd F/U) will begin in 2007 (approximately 2 years after 1st F/U) with support from the Food Allergy Foundation. Relevant data that are being or will be collected at the 1st and 2nd F/U include epidemiologic and dietary questionnaires, anthropometric measures (height, weight; waist and hip circumferences), Tanner Stages, MS phenotypes [total and truncal fat, blood pressure, fasting lipids, fasting and 2-hr post OGTT insulin and glucose), biomarkers (IGF-1, adiponectin, IL-6, TNF-a), Zygosity, and sleep data (questionnaire, 7 day diary, and actigraphy). This proposal seeks support to accomplish the following aims: (1) to measure biomarkers along the major pathways that link SSD with OWO, including Autonomic & Neuroendocrine Function (heart rate variability, cortisol); Inflammation (CRP); and Appetite (leptin, ghrelin) at the 1st and the 2nd follow-up. We will also examine other relevant biomarkers already covered by the funded studies; (2) To conduct cross-sectional and prospective co-twin analyses to determine SSD-OWO relationships; relationships between the biomarkers and OWO; and to examine if the above relationships are genetically mediated and test the modifying effects of age, gender, Tanner stage, physical activity and nutritional status; and (3) To examine whether SSD-OWO relationships are mediated by the biomarkers. The unique opportunities offered by this Chinese twin cohort are: (1) the prospective study design can assess temporal relationships and provide strong evidence for cause-and-effect; (2) the large sample size assures our ability to detect causal associations, unlike most studies in this area, which are underpowered; (3) the co-twin design, in which numerous potential confounding factors-including age, gestational age, pregnancy complications, maternal nutrition, environmental exposure, and parental socioeconomic status-are precisely matched, can minimize confounding in analysis of SSD-OWO associations; (4) the MZ and DZ co-twin models can efficiently partition environmental and genetic contributions to the SSD-OWO relationship; (5) the cost of data collection is largely covered by other funded studies; and (6) the ability to study age groups at particularly high risk for OWO, in which intervention has the greatest potential for life-long improvements in health and well-being. This twin cohort is also a precious resource for future longitudinal studies of sleep and OWO.
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