Medicine and Health Sciences Commons^™

Metabolomic Phenotype Of Hepatic Steatosis And Fibrosis In Mexican Children Living With Obesity, Nayely Garibay-Nieto, Karen Pedraza-Escudero, Isabel Omaña-Guzmán, María José Garcés-Hernández, Eréndira Villanueva-Ortega, Mariana Flores-Torres, José Luis Pérez-Hernández, Mireya León-Hernández, Estibalitz Laresgoiti-Servitje, Juan Carlos Lopez-Alvarenga

School of Medicine Publications and Presentations

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity.

Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. …

Analyzing The Effects Of Body Mass Index In Total Hip Arthroplasty Cases. Does It Influence Patient Characteristics, Operative Planning, And Postoperative Outcomes?, Cesar A. Sevilla Jr, Vanessa Elena Lopez, Mauricio Burbano, Michael Sander

MEDI 9331 Scholarly Activities Clinical Years

Background: Total hip arthroplasty (THA) is one of the most performed orthopaedic procedures commonly used for the treatment of osteoarthritis (OA). There are several underlying factors that lead to the formation of this condition. Not only is obesity one of the main contributors, but it is also a modifiable risk factor and one of the leading causes of end-stage arthrosis of the hip. Though there have been advancements in agricultural and health technologies, rates of obesity continue to rise causing similar increases in the demands for hip replacement surgeries. Therefore, we sought to investigate the effects of BMI on …

Cardiovascular Risk Of Metabolically Healthy Obesity In Two European Populations: Prevention Potential From A Metabolomic Study, Dongmei Wei, Vannina González Marrachelli, Jesus D. Melgarejo, Chia-Te Liao, Angie Hu, Stefan Janssens, Peter Verhamme, Lucas Van Aelst, Thomas Vanassche, Josep Redon

School of Medicine Publications and Presentations

Background

A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern.

Methods

This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood …

Maternal Obesity And Gut Microbiota Are Associated With Fetal Brain Development, Sanjay Basak, Ranjit K. Das, Antara Banerjee, Sujay Paul, Surajit Pathak, Asim K. Duttaroy

Health & Biomedical Sciences Faculty Publications and Presentations

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother's gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological …

Lipoprotein Profiles Of Fat Distribution And Its Association With Insulin Sensitivity, Dongmei Wei, Vannina González Marrachelli, Jesus D. Melgarejo, Chia-Te Liao, Stefan Janssens, Peter Verhamme, Thomas Vanassche, Lucas Van Aelst, Daniel Monleon, Josep Redon, Zhen-Yu Zhang

School of Medicine Publications and Presentations

Background: Fat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated.

Methods: In 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. …

Bioactive Food Components And Their Inhibitory Actions In Multiple Platelet Pathways, Diptimayee Das, Shubhamay Adhikary, Ranjit Kumar Das, Antara Banerjee, Arun Kumar Radhakrishnan, Sujay Paul, Surajit Pathak, Asim K. Duttaroy

Health & Biomedical Sciences Faculty Publications and Presentations

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets' hemostatic and non-hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non-hemostatic disease are to be inhibited while leaving the platelet's hemostatic function unaffected. Platelets' anti-aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non-hemostatic activities are not well known. This review describes the hemostatic and non-hemostatic function of human blood …

The Ccr2+ Monocyte Subsets Increase In Obese Boys But Not Girls With Abnormally High Carotid Intima-Media Thickness: A Pilot Study, María José Garcés-Hernández, Karen Pedraza-Escudero, Nayely Garibay-Nieto, Joselin Hernández-Ruiz, Jessica Lakshmi Prieto-Chávez, Lourdes Andrea Arriaga-Pizano, Eréndira Villanueva-Ortega, Galileo Escobedo, Aaron Noe Manjarrez-Reyna, Juan C. Lopez-Alvarenga

School of Medicine Publications and Presentations

The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2⁺ cell percentage and …

Ancestral Diversity Improves Discovery And Fine-Mapping Of Genetic Loci For Anthropometric Traits-The Hispanic/Latino Anthropometry Consortium, Lindsay Fernández-Rhodes, Mariaelisa Graff, Victoria L . Buchanan, Anne E. Justice, Heather M. Highland, Xiuqing Guo, Wanying Zhu, John Blangero, Joanne E. Curran, Ravindranath Duggirala

School of Medicine Publications and Presentations

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS …

Lrg1 Is An Adipokine That Mediates Obesity-Induced Hepatosteatosis And Insulin Resistance, Sijia He, Jiyoon Ryu, Juanhong Liu, Hairong Luo, Ying Lv, Paul R. Langlais, Jie Wen, Feng Dong, Zhe Sun, Ravindranath Duggirala

School of Medicine Publications and Presentations

Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet–induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 …

Scaling A Community-Wide Campaign Intervention To Manage Hypertension And Weight Loss, Belinda M. Reininger, Lisa A. Mitchell-Bennett, Minjae Lee, Paul G. Yeh, Amanda C. Davé, Soo Kyung Park, Tianlin Xu, Alma G. Ochoa-Del Toro

Physician Assistant Studies Faculty Publications and Presentations

Public health impacts can be achieved when evidence-based interventions are implemented to those most in need. Too often implementation never or slowly occurs. The community-wide campaign intervention Tu Salud ¡Si Cuenta! has evidence of improving health outcomes related to chronic disease among low-income, Latinos. Using the RE-AIM Framework, this study examined if the scaled-up version of the intervention is associated with improvements in hypertension and obesity in 12 locations. Each element of the RE-AIM framework was examined. For "Effectiveness," we examined outcomes overall and by implementing location. We used linear and logistic regression to assess if exposure in the intervention …

Association Of Hiv-1 Infection And Antiretroviral Therapy With Type 2 Diabetes In The Hispanic Population Of The Rio Grande Valley, Texas, Usa, Juan Carlos Lopez Alvarenga, Dora A. Martinez, Alvaro Diaz-Badillo, Liza D. Morales, Rector Arya, Christopher Jenkinson, Joanne E. Curran, John Blangero, Ravi Duggirala, Srinivas Mummidi, Ruben D. Martinez

School of Medicine Publications and Presentations

The Rio Grande Valley (RGV) in South Texas has one of the highest prevalence of obesity and type 2 diabetes (T2D) in the United States (US). We report for the first time the T2D prevalence in persons with HIV (PWH) in the RGV and the interrelationship between T2D, cardiometabolic risk factors, HIV-related indices, and antiretroviral therapies (ART). The PWH in this study received medical care at Valley AIDS Council (VAC) clinic sites located in Harlingen and McAllen, Texas. Henceforth, this cohort will be referred to as Valley AIDS Council Cohort (VACC). Cross-sectional analyses were conducted using retrospective data obtained from …

Sacubitril/Valsartan Inhibits Obesity-Associated Diastolic Dysfunction Through Suppression Of Ventricular-Vascular Stiffness, Annayya R. Aroor, Srinivas Mummidi, Juan C. Lopez-Alvarenga, Nitin Das, Javad Habibi, Guanghong Jia, Guido Lastra, Bysani Chandrasekar

School of Medicine Publications and Presentations

Objective: Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan …

Prevalence Of Liver Cirrhosis And Its Association With Obesity Among Hispanics And Mexican Americans: An Evidence Synthesis, Alexa Perlick, Abaigeal Thompson, Colton Wayne, Angel Rendon, Jose Campo Maldonado

MEDI 9331 Scholarly Activities Clinical Years

INTRODUCTION

The obesity epidemic is a growing public health concern. In addition to the already known complications and comorbidities associated with obesity, data suggest that obesity is an independent risk factor for the development of liver disease.^1,2 However, there is a paucity of data regarding the clinical correlation of obesity and cirrhosis in a predominantly Hispanic population of South Texas. The aim of this systematic literature review is to investigate the prevalence of cirrhosis stratified by obesity in Hispanic populations.

MATERIALS AND METHODS

PubMed was used to perform a thorough literature search. The terms liver cirrhosis and obesity were …

Mortality Outcomes In Therapeutic Versus Prophylactic Anticoagulation In Obese Patients In Predominantly Hispanic Population, Dave Patel, Moktar Ahmed Sheikh-Salah, Raul Garcia, Jewel Udenwagu, Jose Campo Maldonado, Christopher Romero

MEDI 9331 Scholarly Activities Clinical Years

Introduction: As of January 26, 2021, there have been 1,988,063 confirmed cases with 34,701 fatalities from COVID-19 in the state of Texas. As the fatalities increased in Rio Grande Valley, there was overwhelming evidence that showed that obesity, an already hypercoagulable state, was a risk factor that contributed to the severity of COVID-19 infection (Sanchis-Gomar, et. Al. 2020). The prevalence of obesity amongst the population in in the RGV presents an opportunity to correlate trends in outcomes with the obese population that are admitted for inpatient management of COVID-19.

Materials and Methods: This retrospective cohort study looks at patient’s electronic …

A Comparison Of The Prevalence Of Cirrhosis In A Hispanic And Non-Hispanic Population Based On Body Mass Index, Alexa Perlick, Abaigeal Thompson, Colton Wayne, Jose Campo Maldonado, Angel Rendon

MEDI 9331 Scholarly Activities Clinical Years

Background and Significance

The obesity epidemic is a growing public health concern. In addition to the already known complications and comorbidities associated with obesity, data suggest that obesity is an independent risk factor for the development of liver disease. ^1,2 However, there is a paucity of data regarding the clinical correlation of obesity and cirrhosis in a predominantly Hispanic population. Therefore, the aim of this study is to investigate the prevalence of cirrhosis stratified by BMI in a predominately Hispanic population.

Materials and Methods

This retrospective single-centered study was approved by the University of Texas Rio Grande Valley institutional ethics …

Retrospective Study Examining Obesity Hypoventilation Syndrome In Covid+ Patients, Lily Chen, Areeb Masood, Ayman Khaddam, Alyssa Chen, Ildiko Lingvay, Henry Kwang

MEDI 9331 Scholarly Activities Clinical Years

Purpose: Coronavirus disease 2019 (COVID-19) has affected millions of people all over the world with worse proven outcomes in those with certain comorbid conditions, such as diabetes, cardiovascular disease, and pulmonary complications. The Rio Grande Valley located in South Texas with a largely Hispanic population has been hit especially hard during this pandemic with over 3,200 virus-related deaths. This region’s high population of diabetic and obese patients is likely correlated with the especially high mortality rate. While it is understood the impact that obesity has on worsening health outcomes, further research is needed to better understand whether more adverse COVID-19 …

Gender-Specific Differences In Clinical And Metabolic Variables Associated With Nafld In A Mexican Pediatric Population, Eréndira Villanueva-Ortega, María José Garcés-Hernández, Arturo Herrera-Rosas, Juan Carlos Lopez Alvarenga, Estibalitz Laresgoiti-Servitje, Galileo Escobedo, Gloria Queipo, Sergio Cuevas-Covarrubias, Guadalupe Nayely Garibay-Nieto

School of Medicine Publications and Presentations

Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD.

Methods: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender.

Results: The mean age was 10.64±2.54 years. The frequency of NAFLD in boys …

Association Of Crebrf Variants With Obesity And Diabetes In Pacific Islanders From Guam And Saipan, Robert L. Hanson, Saied Safabakhsh, Jeffrey M. Curtis, Wen-Chi Hsueh, Lois I. Jones, Tanisha F. Aflague, Jenny Duenas Sarmiento, Satish Kumar, Nicholas B. Blackburn, Joanne E. Curran

School of Medicine Publications and Presentations

Aims hypothesis

Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan.

Methods

CREBRF rs12513649 and rs373863828 were genotyped in 2022 participants in a community-based cross-sectional study designed to identify determinants of diabetes and end-stage renal disease (ESRD). Associations were analysed …

Obese Mice Exposed To Psychosocial Stress Display Cardiac And Hippocampal Dysfunction Associated With Local Brain-Derived Neurotrophic Factor Depletion, Jacopo Agrimi, Cristina Spalletti, Carlotta Baroni, Gizem Keceli, Guangshuo Zhu, Angela Caragnano, Marco Matteucci, Stephen Chelko, Genaro A. Ramirez-Correa

School of Medicine Publications and Presentations

Introduction: Obesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS.

Methods: In adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was …

Genetic Architecture Of Human Obesity Traits In The Rhesus Macaque, Michael J. Raboin, John Letaw, Asia D. Mitchell, David Toffey, Jessica Mckelvey, Charles T. Roberts Jr, Joanne E. Curran, Amanda Vinson

School of Medicine Publications and Presentations

Objective: Whereas the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are nonexistent. This study assessed genetic contributions to spontaneous adiposity in this species.

Methods: Phenotypic variation by age class and sex for BMI, waist to height ratio, waist to thigh ratio, and waist circumference was assessed in 583 macaques. Total and sex-specific heritability for all traits was estimated, including waist to thigh ratio adjusted for BMI, as well as genotypic and phenotypic correlations. In addition, functional genetic variation at BDNF, FTO, LEP, LEPR, MC4R, PCSK1, POMC, and SIM1 was assessed …

Childhood Obesity And Academic Outcomes In Young Adulthood, Igor Ryabov

Sociology Faculty Publications and Presentations

The present study used nationally representative data from the National Longitudinal Study of Adolescent Health (a.k.a., Add Health) to examine the impact of childhood obesity on young adult educational attainment. In addition to weight status, independent variables included race–ethnicity, immigrant generational status, family socio-economic status (SES), preference for overweight and obese friends in school, school socio-economic and race–ethnic composition, and other important predictors. Educational attainment was measured as a categorical variable with the categories reflecting key educational benchmarks: (1) being a high school graduate; (2) having some college education; and (3) having completed a bachelor’s or higher degree. The results …

Obesity And Obesogenic Growth Are Both Highly Heritable And Modified By Diet In A Nonhuman Primate Model, The African Green Monkey (Chlorocebus Aethiops Sabaeus), C. A. Schmitt, S. K. Service, A. J. Jasinska, Thomas D. Dyer, M. J. Jorgensen, R. M. Cantor, G. M. Weinstock, John Blangero, J. R. Kaplan, N. B. Freimer

School of Medicine Publications and Presentations

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity.

STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a …

Assessing Overweight/Obesity, Dietary Habits, And Physical Activity In Hispanic College Students, Ulku S. Karabulut, Zasha Romero, Phillip Conatser, Murat Karabulut

Health & Human Performance Faculty Publications and Presentations

Objectives

Methods

Results

Association Of Interleukin-6 Polymorphisms With Obesity Or Metabolic Traits In Young Mexican-Americans, K. Boeta-Lopez, J. Duran, D. Elizondo, E. Gonzales, Anne R. Rentfro, Andrea E. Schwarzbach, Saraswathy Nair

Health & Biomedical Sciences Faculty Publications and Presentations

Objective The objective of the study is to investigate the association of interleukin-6 (IL6) promoter single-nucleotide polymorphisms rs1800797 (-597 G/A) and rs1800796 (-572 G/C) with obesity or metabolic syndrome in Mexican-Americans.

Methods The rs1800797 and rs1800796 single-nucleotide polymorphisms were genotyped in Mexican-Americans (n = 437) from South Texas, and results were correlated with measures of obesity and metabolic syndrome including body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, liver enzymes, plasma IL6 and high-sensitive C-reactive protein (hs-CRP).

Results Significant associations were found for the rs1800796 variant with increased waist circumference, insulin resistance, lower IL6 levels and higher hs-CRP …

Genetic Association Analysis Of Polymorphisms In Psd3 Gene With Obesity, Type 2 Diabetes, And Hdl Cholesterol, Shaoqing Gong, Chun Xu, Liang Wang, Ying Liu, Daniel Owusu, Beth A. Bailey, Yujing Li, Kesheng Wang

Health & Biomedical Sciences Faculty Publications and Presentations

Highlights

• First study of PSD3 gene with obesity, type 2 diabetes and HDL cholesterol.

• Identified 23 SNPs associated with obesity with p < 0.05 in gene discovery.

• 20 SNPs were associated with obesity in meta-analysis of two samples.

• 6 SNPs associated with type 2 diabetes and 11 associated with HDL.

• Findings offer new insights into the pathogenesis of obesity and diabetes.

Abstract

Background

The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level.

Methods

Multiple …

Multiethnic Genome-Wide Meta-Analysis Of Ectopic Fat Depots Identifies Loci Associated With Adipocyte Development And Differentiation, Audrey Y. Chu, Xuan Deng, Virginia A. Fisher, Alexander Drong, Yang Zhang, Mary F. Feitosa, Ching-Ti Liu, Olivia Weeks, Audrey C. Choh, Qing Duan, Thomas D. Dyer

School of Medicine Publications and Presentations

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men for six ectopic fat traits in European, African, Hispanic, and Chinese ancestry populations, with and without sex stratification. In total, 7 new loci were identified in association with ectopic fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; PATXN1 and UBE2E2 …

Genome-Wide Meta-Analysis Of 241,258 Adults Accounting For Smoking Behaviour Identifies Novel Loci For Obesity Traits, Anne E. Justice, Thomas W. Winkler, Mary F. Feitosa, Misa Graff, Virginia A. Fisher, Kristin Leonard, Kristin Young, Llilda Barata, Xuan Deng, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an …

Methylation Of Socs3 Is Inversely Associated With Metabolic Syndrome In An Epigenome-Wide Association Study Of Obesity, Omar Ali, Diana Cerjak, Jack W. Kent Jr, Roland James, John Blangero, Melanie A. Carless, Yi Zhang

School of Medicine Publications and Presentations

Epigenetic mechanisms, including DNA methylation, mediate the interaction between gene and environment and may play an important role in the obesity epidemic. We assessed the relationship between DNA methylation and obesity in peripheral blood mononuclear cells (PBMCs) at 485,000 CpG sites across the genome in family members (8-90 y of age) using a discovery cohort (192 individuals) and a validation cohort (1,052 individuals) of Northern European ancestry. After Bonferroni-correction (Pα=0.05 = 1.31 × 10-7) for genome-wide significance, we identified 3 loci, cg18181703 (SOCS3), cg04502490 (ZNF771), and cg02988947 (LIMD2), where methylation status was associated with body mass index percentile (BMI%), a …

Genome-Wide Association Studies Suggest Sex-Specific Loci Associated With Abdominal And Visceral Fat, Yun Ju Sung, L. Pérusse, M. A. Sarzynski, M. Fornage, S. Sidney, B. Sternfeld, T. Rice, J. G. Terry, D. R. Jacobs Jr., John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Background:

To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).

Subjects and Methods:

Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. …

Transcriptomics In Type 2 Diabetes: Bridging The Gap Between Genotype And Phenotype, Christopher Jenkinson, Harald H. H. Goring, Rector Arya, John Blangero, Ravindranath Duggirala, Ralph A. Defronzo

School of Medicine Publications and Presentations

Type 2 diabetes (T2D) is a common,multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits. Transcriptomic analysis bridges the gulf between GWAS and physiological studies. Recent GWAS …