Background: The obesity epidemic is the greatest public health problem of our time, and exerts an enormous health and economic burden by acting as a risk factor for multiple disorders and all-cause mortality. While environmental and social factors certainly contribute to the complex etiology of obesity, there is strong evidence of a substantial genetic component. The majority of obesity genes are involved the leptin-melanocortin receptor pathway governing energy homeostasis, but mutations affecting this circuit are often untreatable and rare, and an improved understanding of other genetic risk factors could aid in the development of novel therapies. In this thesis I study two obesity candidate genes with unclear direct relevance to disease: 1) rare structural variation at the 16p11.2 BP4-BP5 locus and 2) common variation in the Fat Mass and Obesity-Associated (FTO) gene. Methods: 1) I analyzed disinhibited eating measurements from families with 16p11.2 copy number variation (CNV) carriers, to test whether eating in the absence of hunger (EAH) and loss of control (LOC) eating behaviors mediate the dosage-dependent CNV-BMI relationship. 2) Using association data from a study of over 20,000 African Americans and 1,145 functional annotations from the Encyclopedia of Non-coding Elements (ENCODE) and Roadmap Epigenomics projects, I statistically fine-mapped the FTO locus to identify the SNP(s) and cellular contexts underlying the association between FTO and obesity. Results: 1) EAH due to external triggers mediates over 30% of the 16p11.2 deletion’s effect on obesity, while other EAH and LOC behaviors were not significant mediators. This result was independent of IQ deficits and autism related to the CNV, as well as parents’ feeding behaviors and practices. 2) Given 51 FTO SNPs’ association statistics, correlation, and overlap with functional annotations, rs9927317 and rs62033405 had the highest posterior probability of association with obesity. Obesity-associated SNPs may regulate expression of FTO and/or nearby genes through the activity of enhancers and 5’ ends of transcribed genes in the substantia nigra of the brain, bone chondrocytes, and white adipose. Conclusions: These results may help pinpoint the specific genes, regulatory elements, and cellular contexts through which the 16p11.2 and FTO loci exert their effects on obesity.

COVID-19 continues to have a major impact on US health and society. Robust research on the epidemiology of acute and post-acute COVID-19 remains fundamentally important to informing policy makers, scientists, as well as the public. This dissertation reports on the development of a large, diverse, United States general population-based meta-cohort with standardized, prospective ascertainment of SARS-CoV-2 and COVID-19, integrated with comprehensive pre-pandemic phenotyping from 14 extant cohort studies. Meta-cohort data were used to investigate risk and resilience factors for incident severe (hospitalized or fatal) and non-severe COVID-19 and correlates of time-to-recovery from SARS-CoV-2 infection. Results support the major acute and post-acute public health impact of COVID-19 and the vital role of modifiable (e.g., obesity, diabetes, cardiovascular disease) and non-modifiable (e.g., age, sex) risk factors for adverse COVID-19 outcomes. Findings suggest that standard primary care interventions—including obesity and cardiometabolic disease prevention and treatment, depression care, and vaccination—remain fundamental to COVID-19 risk mitigation among US adults. Given its longitudinal design and comprehensive pre-pandemic and pandemic-era measurements, the meta-cohort is well suited to support ongoing work regarding the public health impact of SARS-CoV-2 infection, COVID-19, post-acute sequelae, and pandemic-related social and behavioral changes across multiple health domains.

Introdução: Idosos passam a maior parte do dia em comportamento sedentário. Apesar dessa alta exposição, o impacto do comportamento sedentário na saúde dessa população ainda não foi aprofundado. Objetivo: Revisar sistematicamente as evidências de associação entre o comportamento sedentário e desfechos relacionados à saúde de idosos acima de 60 anos de idade. Métodos: Foram revisadas as bases de dados Medline, Embase, Lillacs, Web of Science, SportsDiscus, PsychInfo, Cinahl e Sedentary Behavior Research Database por estudos observacionais publicados até o mês de maio de 2013, bem como os membros do Sedentary Behaviour Research Network, para identificar artigos potencialmente elegíveis. Após a inclusão, a qualidade metodológica da evidência de cada estudo foi avaliada, utilizando-se o GRADE. Resultados: Foram identificados 23 artigos elegíveis, dos quais apenas 2 (8%) apresentaram alta qualidade de evidência. O tempo gasto em comportamento sedentário foi relacionado a um aumento no risco de mortalidade por todas as causas. Estudos com qualidade moderada de evidências indicaram relação entre o comportamento sedentário e síndrome metabólica, circunferência da cintura e excesso de peso/obesidade. Os resultados de outros desfechos como saúde mental e câncer de rim ainda são insuficientes para conclusões definitivas. Conclusão: Esta revisão sistemática defende a relação entre o comportamento sedentário e aumento da mortalidade em idosos. Futuros estudos com alta qualidade metodológica serão necessários para a verificação de demais desfechos em saúde e para a criação de diretrizes e recomendações sobre comportamento sedentário de idosos / Background: In the last decade, sedentary behavior has emerged as a new risk factor for health. The elderly spend most of their awake time in sedentary activities. Despite this high exposure, the impact of this sedentary behavior on the health of this population has not yet been reviewed. Purpose: We systematically reviewed evidence for associations between sedentary behavior and multiple health outcomes in adults over 60 years of age. Methods: We searched the Medline, Embase, Web of Science, SportsDiscus, PsycInfo, Cinahl, LILACS, and Sedentary Research Database for observational studies published up to May 2013. Additionally, we contacted members of the Sedentary Behaviour Research Network to identify articles that were potentially eligible. After inclusion, the methodological quality of the evidence was assessed in each study. Results: We included 24 eligible articles in our systematic review, of which only 2 (8%) provided high-quality evidence. Greater sedentary time was related to an increased risk of all-cause mortality in the older adults. Some studies with a moderate quality of evidence indicated a relationship between sedentary behavior and metabolic syndrome, waist circumference, and overweightness/obesity. The findings for other outcomes such as mental health and renal cancer cells remain insufficient to draw conclusions. Conclusion: This systematic review supports the relationship between sedentary behavior and mortality in older adults. Additional studies with high methodological quality are still needed to develop informed guidelines for addressing sedentary behavior in older adults

Introdução: Idosos passam a maior parte do dia em comportamento sedentário. Apesar dessa alta exposição, o impacto do comportamento sedentário na saúde dessa população ainda não foi aprofundado. Objetivo: Revisar sistematicamente as evidências de associação entre o comportamento sedentário e desfechos relacionados à saúde de idosos acima de 60 anos de idade. Métodos: Foram revisadas as bases de dados Medline, Embase, Lillacs, Web of Science, SportsDiscus, PsychInfo, Cinahl e Sedentary Behavior Research Database por estudos observacionais publicados até o mês de maio de 2013, bem como os membros do Sedentary Behaviour Research Network, para identificar artigos potencialmente elegíveis. Após a inclusão, a qualidade metodológica da evidência de cada estudo foi avaliada, utilizando-se o GRADE. Resultados: Foram identificados 23 artigos elegíveis, dos quais apenas 2 (8%) apresentaram alta qualidade de evidência. O tempo gasto em comportamento sedentário foi relacionado a um aumento no risco de mortalidade por todas as causas. Estudos com qualidade moderada de evidências indicaram relação entre o comportamento sedentário e síndrome metabólica, circunferência da cintura e excesso de peso/obesidade. Os resultados de outros desfechos como saúde mental e câncer de rim ainda são insuficientes para conclusões definitivas. Conclusão: Esta revisão sistemática defende a relação entre o comportamento sedentário e aumento da mortalidade em idosos. Futuros estudos com alta qualidade metodológica serão necessários para a verificação de demais desfechos em saúde e para a criação de diretrizes e recomendações sobre comportamento sedentário de idosos / Background: In the last decade, sedentary behavior has emerged as a new risk factor for health. The elderly spend most of their awake time in sedentary activities. Despite this high exposure, the impact of this sedentary behavior on the health of this population has not yet been reviewed. Purpose: We systematically reviewed evidence for associations between sedentary behavior and multiple health outcomes in adults over 60 years of age. Methods: We searched the Medline, Embase, Web of Science, SportsDiscus, PsycInfo, Cinahl, LILACS, and Sedentary Research Database for observational studies published up to May 2013. Additionally, we contacted members of the Sedentary Behaviour Research Network to identify articles that were potentially eligible. After inclusion, the methodological quality of the evidence was assessed in each study. Results: We included 24 eligible articles in our systematic review, of which only 2 (8%) provided high-quality evidence. Greater sedentary time was related to an increased risk of all-cause mortality in the older adults. Some studies with a moderate quality of evidence indicated a relationship between sedentary behavior and metabolic syndrome, waist circumference, and overweightness/obesity. The findings for other outcomes such as mental health and renal cancer cells remain insufficient to draw conclusions. Conclusion: This systematic review supports the relationship between sedentary behavior and mortality in older adults. Additional studies with high methodological quality are still needed to develop informed guidelines for addressing sedentary behavior in older adults

BACKGROUND: China has seen rapid increase in obesity and hypertension prevalence and fast food consumption over the past decade. We examined status and risk factors for Western- and Chinese fast food consumption and their associations with health outcomes in Chinese children, and examined how maternal factors were associated with child health outcomes. METHODS: Data of 1626 students aged 7-16 (11.6 ± 2.0) years and their parents in four mega-cities across China (Beijing, Shanghai, Nanjing, and Xi'an) were collected in the 2015 baseline survey of the Childhood Obesity Study in China Mega-cities. Weight, height, waist circumference, and blood pressure were measured. Food intake was assessed using questionnaire. Mixed models were used to examine the associations. RESULTS: Among the children, 11.1% were obese, 19.7% were centrally obese, and 9.0% had hypertension. Obesity prevalence was much higher in boys than in girls (15.2% vs. 6.9% and 27.4% vs. 11.7%, respectively, both P < 0.001). About half (51.9% and 43.6%) of children consumed Western and Chinese fast food, respectively, over the past 3 months. Compared to those with college or above maternal education level, those with elementary school or below maternal education level were 49% more likely to consume Western fast food (odds ratio [OR] and 95% confidence interval [CI]: 1.49 [1.10-2.03]). Chinese fast food consumption rate increased by 12% with each year of increase in child's age (OR and 95% CI: 1.12 [1.02-1.23]). No significant associations between fast food consumption and health outcomes were detected. Adjusting for Western fast food consumption, children with lower maternal education were 71% and 43% more likely to have obesity and central obesity (ORs and 95% CIs: 1.71 [1.12-2.61] and 1.43 [1.00-2.03], respectively), and maternal body mass index was positively associated with child obesity, central obesity, and hypertension (ORs and 95% CIs: 1.11 [1.06-1.17], 1.12 [1.07-1.17], and 1.09 [1.03-1.15], respectively). Results were similar when Chinese fast food consumption was adjusted for. CONCLUSIONS: The prevalence of fast food consumption, obesity and hypertension is high among children in major cities in China. Maternal factors affect child outcomes.