ASSOCIATIONS OF ADIPOSITY PHENOTYPES WITH GENETIC ANCESTRY, GLUCOSE METABOLISM, AND DIET QUALITY IN THE MULTIETHNIC COHORT ADIPOSITY PHENOTYPE STUDY

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2022

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Obesity is associated with adverse health outcomes such as cardiovascular disease, diabetes, and multiple cancers. While body mass index is commonly used as a measure of obesity, measures of body fat distribution through imaging techniques such as magnetic resonance imaging and dual energy x-ray absorptiometry scans have shown that certain types of fat (trunk and abdominal visceral fat) have been associated with greater likelihood of developing certain obesity-related diseases compared to increasing total body weight. Just as race/ethnicity contributes to health disparities, racial/ethnic differences in body fat distribution have been documented but more work is needed to evaluate admixed individuals. In-2013-2016, 1861 non-smoking Multiethnic Cohort participants returned for a clinic visit in which study participants donated fasting blood samples and completed body fat quantification for the Multiethnic Cohort Adiposity Phenotype Study. Using this study, three aims are presented in this dissertation: 1. To explore the association between genetic ancestry proportions with five adiposity phenotypes (total fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), VAT/SAT, and liver fat) and muscle mass index. 2. To evaluate the association between genetic ancestry proportions and type 2 diabetes (T2D) status to determine if the relationship is similar or different as the relation of self-reported race/ethnicity with VAT/SAT as a mediator. 3. To study the additive effect of the genetic ancestry proportions and diet quality as measured by the Healthy Eating Index 2015 (HEI-2015) on VAT and VAT/SAT. In this study, the first aim found that genetic ancestry proportions were associated with adiposity. African genetic ancestry was associated with lower VAT and higher SAT. Among self-reported African American participants, higher proportions of African genetic ancestry were associated with greater muscle mass index. Main Islands Japanese genetic ancestry was associated with lower VAT/SAT, but Okinawan Japanese genetic ancestry was associated with higher VAT/SAT among self-reported Japanese American participants. Of the self-reported Native Hawaiian participants, Native Hawaiian genetic ancestry was associated with total fat mass, VAT, SAT, and muscle mass index. In the second aim, higher Main Islands Japanese and Okinawan Japanese genetic ancestries were associated with higher odds of T2D whereas Southern European and Northern European genetic ancestries were associated with lower odds of T2D. Furthermore, the presence of increased VAT/SAT contributes to the statistically significant associations of African, Main Islands Japanese, Okinawan Japanese, and Native Hawaiian genetic ancestries on fasting blood glucose and homeostatic model assessment for insulin resistance (HOMA-IR). In the third aim, better diet quality was associated with lower VAT and VAT/SAT for self-reported Native Hawaiian and Japanese American participants. Lastly, there is a weak additive effect of African, Main Islands Japanese, and Okinawan Japanese genetic ancestries and HEI-2015 on VAT and VAT/SAT.

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Epidemiology, Adiposity Phenotypes, Diabetes Status, Genetic Ancestry, Healthy Eating Index-2015, Multiethnic Cohort

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86 pages

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