Genomics and Epidemiology: Diverse Measures and Populations in the Trans-Ethnic Fine-Mapping of Genetic Loci for Body Mass Index Public Deposited

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  • March 20, 2019
Creator
  • Fernandez-Rhodes, Lindsay
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Obesity is a global epidemic with concerning disparities in burden across United States (US) racial/ethnic groups. In the absence of measured body weight, self-reports are a commonly used proxy in epidemiologic research. Previous studies have found that self-reported body weight may, on average, underestimate weight. However, this research may not apply to US Hispanics/Latinos, many of whom are recent immigrants from Latin America. We investigated whether self-reported weight was an accurate proxy of measured weight in a sample of Hispanic/Latinos from various Hispanic/Latino backgrounds sampled as part of the baseline examination (2008-2011) of the Hispanic Community Health Study/Study of Latinos. We observed that self-reported weight was an accuracy proxy of measured weight (r2=0.95, average 0.3 kg over-reporting of weight), but differential patterns of misreporting were evident by age, gender, body mass index (BMI) categories, nativity, study site by background, unit of self-reported weight and end digit preference. Numerous studies of obesity in primarily non-Hispanic/Latino European descent populations have identified more than >100 BMI loci. However, these loci collectively explain a fraction of the estimated heritability of BMI perhaps, in part, due to the limited racial/ethnic diversity of the previous samples. I addressed this research gap by generalizing nearly a quarter of previously reported SNP-BMI associations and >80% of 36 fine-mapped BMI loci to racially/ethnically diverse US populations and then by trans-ethnically fine-mapping the underlying functional variants at these loci in a sample of approximately 102,000 African, Hispanic/Latino, Asian, European and American Indian/Alaskan Native descent adults from the Population Architecture using Genomics and Epidemiology Study. These findings will help prioritize the putative functional variants for targeted molecular follow-up and gene-environment interaction studies. In light of the current mismatch between the mounting body of genetic epidemiologic evidence and the populations most burdened by obesity, this research highlighted the utility of alternative measures, such as self-reported weight, and diverse populations in the search for the underlying functional genetic variants for obesity risk. As such, this work serves as a foundation for a wide-range of future research on the complex genetic and environmental determinants of obesity in US populations, like Hispanic/Latinos.
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  • In Copyright
Advisor
  • Robinson, Whitney
  • Gordon-Larsen, Penny
  • North, Kari
  • Smokowski, Paul
  • Franceschini, Nora
Degree
  • Doctor of Public Health
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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