Medical Sciences Commons^™

Gene By Environment Interaction And Metabolic-Associated Fatty Liver Disease In Mexican American Patients With Depression, Khalid Sheikh, Vincent P. Diego, Sandra L. Laston, Eron G. Manusov, Sarah Williams-Blangero, John Blangero

Research Colloquium

Knowledge of genetic and environmental (G x E) interaction effects on metabolic-associated fatty liver disease (MAFLD) is limited. The purpose of this study was to examine the impact of G x E interaction effects on MAFLD in Mexican Americans in the Rio Grande Valley (RGV). The environment examined was depression as measured by the Beck Depression Inventory-II (BDI-II). We examined potential G x E interaction in the phenotypic expression of MAFLD, including hepatic steatosis and hepatic fibrosis, using variance component models and likelihood-based statistical inference. Significant G x E interactions were identified for hepatic fibrosis x BDI-II. These findings provide …

Unraveling The Mechanisms By Which Smoking And Alcohol Alter Pancreatic Cancer Pathogenesis, Poornima Devi Shaji, Ana Martinez Bulnes, Vincent P. Diego, Subhash C. Chauhan, Sheema Khan

Research Symposium

Pancreatic cancer is the 3^rd leading cause of cancer in United States with a 5-to-7-year relative survival rate. This can be attributed to the late onset of symptoms and diagnosis of the disease, which makes it unmanageable at its later stage. Ethnic differences in pancreatic cancer incidence have been reported, especially regarding higher incidence in African Americans. African Americans are more likely than Asian, Hispanic, or whites’ people to develop pancreatic cancer. They have highest incidence rate between 28% and 59% higher than other racial groups. The mortality rate for Blacks is 13.3 per 100,000 people, while for Whites …

Thermal Dose Inactivation Of Escherichia Coli By Magnetic Induced Hyperthermia, Silverio A. Lopez, Carlos Trevino De Leo, Ivan Davila, Karen S. Martirosyan

Research Symposium

Background: Apoptosis of mutated cells via magnetic hyperthermia has gained advocacy as technology capable of being used in lieu of chemotherapy for targeting cancer tumors. Progress of nanotechnology offers effective remote heating of magnetic fluid via hyperthermia. The heating and specific power absorption of these nanoparticles use in the magnetic fluid are dependent on particle properties and treatment locations.

Methods: Nanoparticles were fabricated using microfluidic system by interaction of two solutions containing 2Fe(NO3)3+FeSO4 and NaOH+2%Dextran to create nanostructured media with a biocompatible dextran coating and a Fe3O4 core. The nanoparticles, of a concentration of 5mg/ml, were placed in a vile …

The Role Of Zinc In Psd-95 Palmitoyl Modification, Luis F. Acosta, Lili Guerra, Safiya Syed, Ivonn Ruvalcaba, Yonghong Zhang, Xiaoqian Fang

Research Symposium

Postsynaptic density-95 (PSD-95) is a membrane-associated guanylate kinase that mediates localization of receptors in the excitatory postsynaptic density. It has been reported that PSD-95 mediates postsynaptic localization of NMDA receptors and anchors postsynaptic AMPAR receptors mainly through its postsynaptic membrane targeting by its N-terminal palmitoylation. Recent studies have shown that Ca2+/calmodulin blocks palmitoylation of PSD-95 by binding at the N-terminus of PSD-95, which promotes dissociation of PSD-95 from the postsynaptic membrane and causes loss of surface AMPARs in cultured neurons. Another metal ion zinc is found in various areas of the brain. As an endogenous neuromodulator, zinc plays a role …

Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel

Research Symposium

Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.

Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.

Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …

Fornix Volumetric Increase During Aging Associates To Microglia Activation Leading To Defective Cognitive Performance, Marcela Cárdenas Tueme, Luis Ángel Trujillo-Villarreal, Victor Ramírez-Amaya, Eduardo Garza-Villarreal, Alberto Camacho-Morales, Diana Reséndez-Pérez

Research Symposium

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.

Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines …

Diverse Tregs Population And Effects Of Their Inhibition On Growth Of Oral Cancer Cells, Sadhna Aggarwal, Satya N. Das, Suresh C. Sharma

Research Symposium

Oral squamous cell carcinoma (OSCC) is one of the major cancers affecting in Asian countries. The main causative factor has been tobacco habit. It has been reported that immune dysfunction in these patients is one of the major factors for tumor growth and dissemination that affects disease free survival of the patients.

We assessed the phenotypic and functional characteristics of Regulatory T (Treg) CD4+CD25+FoxP3+subsets in patients with OSCC by multicoloured flow cytometry. Subsequently we investigated the effects their inhibition via TDG on growth of OSCC cell lines in vitro.

An increased (p

Hence, it seems reasonable to assume that modulation …

Variant Of Fii Gene Plays A Critical Role In Coagulation Potential In Mexican-Americans, Hoang Anh T. Nguyen, Shuchita Vijay Jhaveri, Marcio A. Almeida, Vincent P. Diego, Satish Kumar, Juan M. Peralta, Joanne E. Curran, Bernadette W. Luu, Donna M. Lehman, Ralph A. Defronzo, Laura Almasy, Sarah Williams-Blangero, Ravi Duggirala, John Blangero, Tom Howard

Research Symposium

Background: Disruption in the balance between coagulation and bleeding can result in varying phenotypes such as hypercoagulability and can lead to the development of cardiovascular disease. In our study utilizing extended families of Mexican-Americans from South Texas, we performed a search for protein-altering variants influencing coagulation potential.

Methods: Mexican-Americans in the study were genotyped using Illumina-(human)-exome-24 chip to screen for protein-altering variants. Variants were analyzed for their association with FII activity, aPTT, and PT. Linear-mixed-model analysis was performed to estimate trait heritabilities and to interrogate single nucleotide variations (SNV) for evidence of genetic association. To control for multiple testing, associations …

Whole Genome Sequence Data Implicate Rbfox1 In Epilepsy Risk In Baboons, Mark Z. Kos, Melanie A. Carless, Lucy Blondell, Mary M. Leland, Koyle D. Knape, Harald H. H. Goring, Charles A. Szabo

Research Symposium

Background: Baboons exhibit a genetic generalized epilepsy (GGE) that resembles juvenile myoclonic epilepsy and may represent a suitable genetic model for human epilepsy. The genetic underpinnings of epilepsy were investigated in a baboon colony at the Southwest National Primate Research Center (San Antonio, TX) through the analysis of whole-genome sequence (WGS) data.

Methods: Baboon WGS data were obtained for 38 cases and 19 healthy controls from the NCBI Sequence Read Archive and, after standard QC filtering, two subsets of variants were examined: (1) 20,881 SNPs from baboon homologs of 19 candidate GGE genes; and (2) 36,169 protein-altering SNPs. Association tests …

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Years Of Education And Total Intracranial Volume: A Longitudinal Study, Okechukwu C. Erinne

Research Symposium

Background: Education is one of the factors that contribute to a higher brain reserve. Based on the brain reserve hypothesis, the greater the brain reserve, the less likely it is to develop a neurocognitive disorder, such as dementia.

Methods: Data for this study were obtained from the Open Access Series of Imaging Studies (OASIS) longitudinal magnetic resonance imaging (MRI) data in nondemented and demented adults. There was a total of 150 right-handed participants and 373 imaging sessions, with an average duration of 719 days between visits. The primary outcome was estimated total intracranial volume (eTIV). Multivariable longitudinal regression was used …

Alzheimer’S Disease Studies In The Tex-Mex Border: Dissecting A Complex Multifactorial Problem, Ney Alliey-Rodriguez, Rosa V. Pirela, Alvaro Diaz-Badillo, Karla Lopez Lorenzo, Noe Garza, Frank Gilliam, Eron G. Manusov, Gladys E. Maestre

Research Symposium

Purpose: Alzheimer’s Disease (ALZ) is the leading cause of dementia in the aging population, and Latinos have >3 times higher risk to develop dementia than the overall US population. Although several studies have examined for possible causes of this increased risk, lack of comprehensive information plus a reduced number of Latino samples available in each study have hindered the answers.

Description: The University of Texas Rio Grande Valley has joined two large studies looking for multiple biomarkers associated with ALZ: The South Texas Alzheimer’s Center Clinical Data Repository and Biobank (STAC) and the Texas Alzheimer’s Research and Care Consortium (TARCC). …

Understanding The Resources, Barriers, Facilitators And Interests About Aging And Dementia Research Of Community Members From The Rio Grande Valley, Karla Daniela Lopez Lorenzo, Rosa V. Pirela Mavarez, Gabriela Osuna, Kendra Stine, Nathalie Chacon, Noe Garza, Gladys E. Maestre

Research Symposium

Background: One of ten people aged 65 develops Alzheimer’s Disease and it is one of the sixth-leading cause of death in the United States. The Rio Grande Valley (RGV) is mostly constituted by Hispanic/Latinos (93%), a population that has a 1.5X increased risk of AD onset. Nevertheless, there are not enough resources to support people living with dementia and their care partners. This study will leverage research efforts deployed by the RGV Alzheimer’s Disease Resource Center for Minority Aging Research to understand the social representations about the resources, barriers, facilitators, and interests of the RGV community about dementia and Alzheimer’s …

Comparing Stroke Symptom Recognition And Intervention Times In The Rio Grande Valley, Joshua M. Ninan, Kelsey Baker

Research Symposium

This is a retrospective study that aims to evaluate the duration from onset of stroke-like symptoms to presentation to medical facilities for aid in the Rio Grande Valley. The main goal of the study is to understand the extent of pre-hospital delays with regards to the treatment of stroke in the RGV.

Pro- And Anti-Inflammatory Biomarkers As Predictors Of Response To Valproate In Patients With Comorbid Alcohol Use And Bipolar Disorder-Preliminary Findings, Ilya Blokhin, Lisa Harlow, Eleonore Beurel, Feng Miao, Dana Ascherman, Claes Wahlestedt, Ihsan Salloum

Research Symposium

Objective/Hypothesis: Bipolar disorder (BD) has the highest association with alcohol and other substance use disorders compared to other major psychiatric disorders. This patient population is particularly challenging to treat. We have previously shown that some patients with co-occurring alcohol use and bipolar disorders respond to the GABAergic agonist valproate (VPA), which is known to modulates the dopaminergic system, and also as an epigenetic modifier. Predictors of therapeutic response to VPA in patients with AUD/BD are not known, and the subgroup which would benefit from VPA is still to be identified. Recent evidence suggests that AUD promotes a pro-inflammatory state while …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Can Alternative Medical Methods Evoke Neuro-Functional Somatosensory Responses? A Case Study Suggesting Functional Improvement, Alhasn Otaif, Mashan E. Alshammari, Christine G. Gerin

Research Symposium

Somatosensory pathways act as the avenue in transferring information concerning the body and its interaction with the external environment to the brain. We aim to demonstrate that through studying somatosensory, motor cortical and subcortical networks, we can explain functional recovery after stimulations applied as an alternative medical treatment. Those stimulations might have evidenced neural pathways and networks important in recovery of function. Materials and methods: The de-identified medical reports of nine patients with initial presentations of cerebral trauma or stroke inducing paralysis were studied.These included the alternative treatments they received and other available materials such as videos and photographs. Patients …

Prevalence Comparison Of Accompanying Lesions Between Primary And Recurrent Anteriordislocation In The Shoulder, Doo-Sup Kim, Changho Yi, Yeo-Seung Yoon

Research Symposium

Background: Many authors have reported the presence of intra-articular lesions after primary dislocation of the shoulder joint. However, few studies have focused on their prevalence or the differences in accompanying lesions between primary and recurrent dislocations of the shoulder joint.

Purpose: This study was undertaken to investigate and analyze accompanying lesions, including types of anteroinferior labrum injuries, using diagnostic arthroscopy and magnetic resonance arthrography (MRA) in 144 patients with traumatic anterior dislocation of the shoulder joint.Study Design: Cohort study; Level of evidence, 3.

Methods: There were 33 patients with 33 dislocations in the primary dislocation group and 111 patients with …

Familial Chylomicronemia Syndrome: A Family Case Report In U.S./Mexico Border By Cediamet, Carlos E. Maldonado, Carlo Hector, Mariana Mendez, Claudia Munguia-Cisneros, Leonel Vela, Juan Carlos Lopez Alvarenga

Research Symposium

Primary familiar hyperchylomicronemia syndrome (FHS) is an extremely rare autosomal recessive condition. In 80% of cases is a result of a mutation in lipoprotein lipase, meanwhile, the 20% is a malfunctioning enzyme due to APOC2, APOA5, LMF1, or GP1HBP1. It is estimated FHS affects 3000 to 5000 individuals globally, with no correlation by sex or race. We are presenting a family with FHS in Reynosa, Mexico.

The index patient was a male 36 years old who attended the CEDIAMET clinic after his 6th episode of acute pancreatitis. He has triglycerides 1300 mg/dl and CT scan with Balthazar C score. He …

Foxo Transcription Factors & Gene Expression, Larissa Barroso, Angelica M. Reyes, David Flores, Millat Jahan, Shania Pintor, Alma Lopez, Megan Keniry

Research Symposium

This paper attempts to highlight ForkHead box transcription factors (FOXO -1, -3, and -4) importance of subcellular localization in U87MG and myoblasts.

Ybx1 Modulates Drug Resistance In Liver Cancer, Ana G. Ayala Pazzi

Research Symposium

According to the Texas Cancer Registry, hepatocellular carcinoma (HCC) is the sixth most common cause of cancer death. In 2015, Texas had the country's highest incidence rate and the fourth highest mortality rate. Texas Hispanics (87% of Mexican origin) showed the highest incidence and mortality rates compared to the overall US Hispanic population, with individuals of Mexican origin having the highest rates. The Rio Grande Valley, which is predominantly Mexican, is extremely affected by this fact, which exacerbates the need to address this issue within our community.

A major challenge in improving patient therapy in liver cancer is Sorafenib resistance. …

Genotype-By-Socioeconomic Status Interaction Influences Heart Disease Risk Scores And Carotid Artery Thickness In Mexican Americans: The Predominant Role Of Education In Comparison To Household Income And Socioeconomic Index, Vincent P. Diego, Eron G. Manusov, Xi Mao, Joanne E. Curran, Harald H. H. Goring, Marcio A. Almeida, Michael Mahaney, Juan M. Peralta, John Blangero, Sarah Williams-Blangero

School of Medicine Publications

Background: Socioeconomic status (SES) is a potent environmental determinant of health. To our knowledge, no assessment of genotype-environment interaction has been conducted to consider the joint effects of socioeconomic status and genetics on risk for cardiovascular disease (CVD). We analyzed Mexican American Family Studies (MAFS) data to evaluate the hypothesis that genotype-by-environment interaction (GxE) is an important determinant of variation in CVD risk factors.

Methods: We employed a linear mixed model to investigate GxE in Mexican American extended families. We studied two proxies for CVD [Pooled Cohort Equation Risk Scores/Framingham Risk Scores (FRS/PCRS) and carotid artery intima-media thickness (CA-IMT)] in …

The Mex-Cog Cognitive Assessment Battery: Discriminant Analysis Of The Cognitive Performance Profile In Older Adults, Silvia Mejia-Arango, Sara Aguilar-Navarro, Alberto José Mimenza-Alvarado

School of Medicine Publications

Objective. To analyze the cognitive profile of a clinical sample using the Mex-Cog cognitive battery and establish which cognitive measures and domains contribute most to group separation.

Materials and methods. A group of 145 older adults previously diagnosed with dementia (n= 47), mild cognitive impairment MCI (n= 47), or as cognitively normal (n= 51) were assessed with the Mex-Cog cognitive battery. Six linear discriminant analyses (LDA) were estimated to compare dementia vs. cognitively normal, MCI vs. cognitively normal, and MCI vs. dementia, using ten individual measures and six cognitive domains. We used a leave-one-out cross-validation procedure to evaluate the predictive …

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Ravi Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …

Qunex—An Integrative Platform For Reproducible Neuroimaging Analytics, Jie Lisa Ji, Jure Demšar, Clara Fonteneau, Zailyn Tamayo, Lining Pan, Aleksij Kraljic, Andraž Matkovic, Nina Purg, Markus Helmer, Anderson M. Winkler

School of Medicine Publications

Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability.

Methods: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a “turnkey” command for the reproducible deployment …

Potential Mirna Biomarkers And Therapeutic Targets For Early Atherosclerotic Lesions, Genesio M. Karere, Jeremy P. Glenn, Ge Li, Ayati Konar, John L. Vandeberg, Laura A. Cox

School of Medicine Publications

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, …

Volume Of Subcortical Brain Regions In Social Anxiety Disorder: Mega-Analytic Results From 37 Samples In The Enigma-Anxiety Working Group, Nynke A. Groenewold, Janna Marie Bas-Hoogendam, Alyssa R. Amod, Max A. Laansma, Laura S. Van Velzen, Moji Aghajani, Kevin Hilbert, Hyuntaek Oh, Ramiro Salas, Anderson M. Winkler

School of Medicine Publications

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven …

Neuroarquitectura: Percepción De Cambios De La Atmósfera, Gladys E. Maestre, Yohany Albornoz

School of Medicine Publications

[Neuroarchitecture: perception of changes in the atmosphere]

Differential Expression Of Interferon-Induced Protein With Tetratricopeptide Repeats 3 (Ifit3) In Alzheimer's Disease And Hiv-1 Associated Neurocognitive Disorders, Armando Garces, Bryan Martinez, Roberto De La Garza, Deepa Roy, Kaylie-Anna Vallee, Jerel Adam Fields, David J. Moore, Hansapani Rodrigo, Upal Roy

Health & Biomedical Sciences Faculty Publications

The United Nations projects that one in every six people will be over the age of 65 by the year 2050. With a rapidly aging population, the risk of Alzheimer's disease (AD) becomes a major concern. AD is a multifactorial disease that involves neurodegeneration in the brain with mild dementia and deficits in memory and other cognitive domains. Additionally, it has been established that individuals with Human Immunodeficiency Virus-1 (HIV-1) experience a 5 to 10-year accelerated aging and an increased risk of developing HIV-associated neurocognitive disorders (HAND). Despite a significant amount of clinical evidence pointing towards a potential overlap between …

Multi-Ancestry Transcriptome-Wide Association Analyses Yield Insights Into Tobacco Use Biology And Drug Repurposing, Fang Cheng, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J. Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Juan M. Peralta

School of Medicine Publications

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with …