Medicine and Health Sciences Commons^™

Sequence Data And Association Statistics From 12,940 Type 2 Diabetes Cases And Controls, Jason Flannick, Christian Fuchsberger, Anubha Mahajan, Tanya M. Teslovich, Vineeta Agarwala, Kyle J. Gaulton, Lizz Caulkins, Rector Arya, Ravi Duggirala, Joanne E. Curran, Satish Kumar, John Blangero

School of Medicine Publications and Presentations

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1–5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency …

Impact Of The G84e Variant On Hoxb13 Gene And Protein Expression In Formalin-Fixed, Paraffin-Embedded Prostate Tumours, Liesel M. Fitzgerald, Kelsie Raspin, James R. Marthick, Matt A. Field, Roslyn C. Malley, Russell J. Thomson, Nicholas B. Blackburn, Erika Banks, Annette Banks, Jac C. Charlesworth, Shaun Donovan, Joanne L. Dickinson

School of Medicine Publications and Presentations

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type …

Exome Sequences Of Multiplex, Multigenerational Families Reveal Schizophrenia Risk Loci With Potential Implications For Neurocognitive Performance, Mark Kos, Melanie A. Carless, Juan M. Peralta, Joanne E. Curran, Ellen E. Quillen, Marcio Almeida, August N. Blackburn, Lucy Blondell, David Roalf, Michael F. Pogue-Geile, Harald H. H. Goring, Laura Almasy

School of Medicine Publications and Presentations

Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based …

Trak2, A Novel Regulator Of Abca1 Expression, Cholesterol Efflux And Hdl Biogenesis, Nicole J. Lake, Rachael L. Taylor, Hugh Trahair, K. N. Harikrishnan, Joanne E. Curran, Marcio Almeida, Hemant Kulkarni, Matthew P. Johnson, Thomas D. Dyer, Michael Mahaney, Harald H. H. Goring, John Blangero

School of Medicine Publications and Presentations

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.

Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the …

Identity-By-Descent Mapping Identifies Major Locus For Serum Triglycerides In Amerindians Largely Explained By An Apoc3 Founder Mutation, Wen-Chi Hsueh, Anup K. Nair, Sayuko Kobes, Peng Chen, Harald H. H. Goring, Toni I. Pollin, Alka Malhotra, William C. Knowler, Leslie J. Baier, Robert L. Hanson

School of Medicine Publications and Presentations

Background—Identity-by-descent (IBD) mapping using empirical estimates of IBD allele sharing may be useful for studies of complex traits in founder populations, where hidden relationships may augment the inherent genetic information that can be used for localization.

Methods and Results—Through IBD mapping, using ~400,000 SNPs, of serum lipid profiles we identified a major linkage signal for triglycerides (TG) in 1,007 Pima Indians (LOD=9.23, p=3.5×10−11 on chromosome 11q). In subsequent fine-mapping and replication association studies in ~7,500 Amerindians, we determined that this signal reflects effects of a loss-of-function Ala43Thr substitution in APOC3 (rs147210663) and 3 established functional SNPs in APOA5. …

Genetic Variation And Gene Expression Across Multiple Tissues And Developmental Stages In A Non-Human Primate, Anna J. Jasinska, Ivette Zelaya, Susan K. Service, Christine B. Peterson, Rita M. Cantor, Oi-Wa Choi, Joseph Deyoung, Eleazar Eskin, Lynn A. Fairbanks, John Blangero, Thomas D. Dyer

School of Medicine Publications and Presentations

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral …

Transition From Pre-Diabetes To Diabetes And Predictors Of Risk In Mexican-Americans, Shenghui Wu, Joseph B. Mccormick, Joanne E. Curran, Susan P. Fisher-Hoch

School of Medicine Publications and Presentations

Background: No studies have examined risk factors for the transition from pre-diabetes to diabetes in populations with widespread obesity and diabetes. We determined proximal changes and factors affecting the transition among Mexican-Americans with pre-diabetes.

Methods: Participants with pre-diabetes (n=285) were recruited from our randomly sampled population-based Cameron County Hispanic Cohort. These participants were followed for an average of 27 months with repeat examination every 3 to 4 months. Metabolic health was defined as having less than 2 metabolic abnormalities (e.g., hypertension, elevated low-density lipoprotein, etc). Diabetes was identified as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% and/or on hypoglycemic …

Rare, Potentially Pathogenic Variants In Znf469 Are Not Enriched In Keratoconus In A Large Australian Cohort Of European Descent, Sionne E. M. Lucas, Tiger Zhou, Nicholas B. Blackburn, Richard A. Mills, Jonathan Ellis, Paul Leo, Emmanuelle Souzeau, Bronwyn Ridge, Jac C. Charlesworth, Matthew A. Brown

School of Medicine Publications and Presentations

Purpose: The Zinc Finger Protein 469 (ZNF469) gene has been proposed as a candidate gene for keratoconus due to the association of an upstream polymorphism (rs9938149) with the disease in two independent studies, and the role of the gene in the autosomal recessive disease Brittle Cornea Syndrome. Coding variants in ZNF469 have been assessed for association with keratoconus in several small studies, with conflicting results. We assessed rare, potentially pathogenic variants in ZNF469 for enrichment in keratoconus patients in a cohort larger than all previous studies combined.

Methods: ZNF469 was sequenced in 385 Australian keratoconus patients of European …

Whole Genome Sequencing In Psychiatric Disorders: The Wgspd Consortium, Stephan J. Sanders, Benjamin M. Neale, Hailiang Huang, Donna M. Werling, Joon-Yong An, Shan Dong, Goncalo Abecasis, P. Alexander Arguello, John Blangero, Michael Boehnke

School of Medicine Publications and Presentations

As technology advances, whole genome sequencing (WGS) is likely to supersede other genotyping technologies. The rate of this change depends on its relative cost and utility. Variants identified uniquely through WGS may reveal novel biological pathways underlying complex disorders and provide high-resolution insight into when, where, and in which cell type these pathways are affected. Alternatively, cheaper and less computationally intensive approaches may yield equivalent insights. Understanding the role of rare variants in the noncoding gene-regulating genome, through pilot WGS projects, will be critical to determine which of these two extremes best represents reality. With large cohorts, well-defined risk loci, …

Sex-Biased Microrna Expression In Mammals And Birds Reveals Underlying Regulatory Mechanisms And A Role In Dosage Compensation, Maria Warnefors, Katharina Mössinger, Jean Halbert, Anja Studer, Tania Studer, John L. Vandeberg, Isa Lindgren, Amir Fallahshahroudi, Per Jensen, Henrik Kaessmann

School of Medicine Publications and Presentations

Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that …

Tc-Ptp Nuclear Trafficking In Keratinocytes, Mihwa Kim, Liza D. Morales, Dae Joon Kim

School of Medicine Publications and Presentations

No abstract provided.

Protein Tyrosine Signaling And Its Potential Therapeutic Implications In Carcinogenesis, Mihwa Kim, Minwoo Baek, Dae Joon Kim

School of Medicine Publications and Presentations

Protein tyrosine phosphorylation is a crucial signaling mechanism that plays a role in epithelial carcinogenesis. Protein tyrosine kinases (PTKs) control various cellular processes including growth, differentiation, metabolism, and motility by activating major signaling pathways including STAT3, AKT, and MAPK. Genetic mutation of PTKs and/or prolonged activation of PTKs and their downstream pathways can lead to the development of epithelial cancer. Therefore, PTKs became an attractive target for cancer prevention. PTK inhibitors are continuously being developed, and they are currently used for the treatment of cancers that show a high expression of PTKs. Protein tyrosine phosphatases (PTPs), the homeostatic counterpart of …

Associations Between Self-Reported Sleep Quality And White Matter In Community-Dwelling Older Adults: A Prospective Cohort Study, Claire E. Sexton, Enikő Zsoldos, Nicola Filippini, Ludovica Griffanti, Anderson M. Winkler, Abda Mahmood, Charlotte L. Allan, Anya Topiwala, Simon D. Kyle, Kai Spiegelhalder

School of Medicine Publications and Presentations

Both sleep disturbances and decline in white matter microstructure are commonly observed in ageing populations, as well as in age-related psychiatric and neurological illnesses. A relationship between sleep and white matter microstructure may underlie such relationships, but few imaging studies have directly examined this hypothesis. In a study of 448 community-dwelling members of the Whitehall II Imaging Sub-Study aged between 60 and 82 years (90 female, mean age 69.2 ± 5.1 years), we used the magnetic resonance imaging technique diffusion tensor imaging to examine the relationship between self-reported sleep quality and white matter microstructure. Poor sleep quality at the time …

Prevalence Of Aflatoxin-Associated Tp53r249s Mutation In Hepatocellular Carcinoma In Hispanics In South Texas, Jingjing Jiao, Weibo Niu, Ying Wang, Keith Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica Michelle Betancourt-Garcia, R. Armour Forse, Joseph B. Mccormick, Susan P. Fisher-Hoch

School of Medicine Publications and Presentations

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation …

Uvb-Induced Nuclear Translocation Of Tc-Ptp By Akt/14-3-3Σ Axis Inhibits Keratinocyte Survival And Proliferation, Mihwa Kim, Liza D. Morales, Minwoo Baek, Thomas J. Slaga, John Digiovanni, Dae Joon Kim

School of Medicine Publications and Presentations

Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. …

“Yes, And …” Exploring The Future Of Learning Analytics In Medical Education, Matt M. Cirigliano, Charlie Guthrie, Martin V. Pusic, Anna T. Cianciolo, Jennifer E. Lim-Dunham, Anderson Spickard Iii, Valerie Terry

School of Medicine Publications and Presentations

This Conversations Starter article presents a selected research abstract from the 2017 Association of American Medical Colleges Northeastern Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the study. Commentators brainstormed “what's next” with learning analytics in medical education, including advancements in interaction metrics and the use of interactivity analysis to deepen understanding of perceptual, cognitive, and social learning and transfer processes.

24-Hour Blood Pressure Variability Assessed By Average Real Variability: A Systematic Review And Meta-Analysis, Luis J. Mena, Vanessa G. Felix, Jesus D. Melgarejo, Gladys E. Maestre

School of Medicine Publications and Presentations

Background-—Although 24-hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24-hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24-hour BPV, including the average real variability (ARV) index.

Methods and Results-—Studies chosen for review were those that presented data for 24-hour BPV in adults from meta-analysis, longitudinal or cross-sectional design, and examined BPV in terms …

Acute Maternal Oxidant Exposure Causes Susceptibility Of The Fetal Brain To Inflammation And Oxidative Stress, Feroz Akhtar, Christopher A. Rouse, Gabriel Catano, Marcus Montalvo, Sarah L. Ullevig, Reto Asmis, Kusum Kharbanda, Shivani K. Maffi

School of Medicine Publications and Presentations

Background

Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive.

Methods

Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) …

Reduction Of Cognitive Decline In Patients With Or At High Risk For Diabetes, Gladys E. Maestre

School of Medicine Publications and Presentations

Purpose of review—The incidence of Alzheimer’s disease and related disorders is expected to triple by 2050. People with type 2 diabetes and prediabetes have a higher risk of cognitive dysfunction, including Alzheimer’s disease and vascular dementia. Controversy remains about when and how to prevent and treat cognitive dysfunction in people with or at high risk of diabetes.

Recent findings—In our review of ongoing clinical trials, we have found that there has been an increase in the number of studies assessing the efficacy of pharmacological and non-pharmacological approaches to prevent or slow down cognitive impairment among people with or …

Benchmarking Relatedness Inference Methods With Genome-Wide Data From Thousands Of Relatives, Monica D. Ramstetter, Thomas D. Dyer, Donna M. Lehman, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Jason G. Mezey, Amy L. Williams

School of Medicine Publications and Presentations

Inferring relatedness from genomic data is an essential component of genetic association studies, population genetics, forensics, and genealogy. While numerous methods exist for inferring relatedness, thorough evaluation of these approaches in real data has been lacking. Here, we report an assessment of 12 state-of-the-art pairwise relatedness inference methods using a data set with 2485 individuals contained in several large pedigrees that span up to six generations. We find that all methods have high accuracy (92–99%) when detecting first- and second-degree relationships, but their accuracy dwindles to76% of relative pairs. Overall, the most accurate methods are Estimation of Recent Shared Ancestry …

Detection And Risk Stratification Of Women At High Risk Of Preterm Birth In Rural Communities Near Nagpur, India, Archana Patel, Amber Abhijeet Prakash, Yamini V. Pusdekar, Hemant Kulkarni, Patricia Hibberd

School of Medicine Publications and Presentations

Background: Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB.

Methods: Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community …

Ontogeny Of Myosin Isoform Expression And Prehensile Function In The Tail Of The Gray Short-Tailed Opossum ( Monodelphis Domestica), Dylan R. Thomas, Brad A. Chadwell, Gary R. Walker, Julio E. Budde, John L. Vandeberg, Michael T. Butcher

School of Medicine Publications and Presentations

Terrestrial opossums use their semiprehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 mo, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3-7 mo) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and -2B, which will transition into greater MHC-1β and -2A isoform content …

The Influence Of Social Isolation And Medical Comorbidities On Geriatric Congestive Heart Failure Hospital Readmissions, Daniel Keyes, Greg Sheremeta, Jerrit Yang, Naomi Davis, Shiling Zhang, Kevin Boehm

School of Medicine Publications and Presentations

CONTEXT

Social isolation and comorbidities are likely to have a significant level of influence on the healthcare use patterns of geriatric patients with ongoing congestive heart failure (CHF)-related needs.

METHODS

A retrospective study was conducted in a specialized emergency department (ED) with a sample of 286 geriatric CHF patients who initially received CHF-related care over a six-month period. Social isolation levels were assessed using a pre-existing four-point screening tool used in the study setting and composite comorbidity was gauged using the Charlson Comorbidity Index method. Subjects were categorized into either “less than 30-day readmission” or “greater than 30-day readmission/non-readmitted” sample …

Inaugural Research Symposium, The University Of Texas Rio Grande Valley. School Of Medicine

School of Medicine Publications and Presentations

Inaugural Research Symposium 2017

A Voice In Your Ear: Podcasts As A Strategy To Support Successful Student Transition Into Medical Education, Michael Lapelusa, Valerie Terry, Arden D. Dingle

School of Medicine Publications and Presentations

A Voice in Your Ear: Podcasts as a Strategy to Support Successful Student Transition into Medical Education Michael LaPelusa, Valerie Terry, Ph.D., Arden Dingle, M.D. Background The University of Texas Rio Grande Valley (UTRGV) School of Medicine (SOM) welcomed their first student cohort in July 2016 (Class of 2020). In July 2017, the SOM will matriculate their second cohort (Class of 2021). To organize information and advice from the Class of 2020 to the Class of 2021 in an innovative and practical manner, a series of student-created podcasts is being developed to deliver their "words of wisdom." A key aim …

Optimal Echo Time For Functional Mri Of The Infant Brain Identified In Response To Noxious Stimulation, Sezgi Goksan, Caroline Hartley, Samuel A. Hurley, Anderson M. Winkler, Eugene P. Duff, Mark Jenkinson, Richard Rogers, Stuart Clare, Rebeccah Slater

School of Medicine Publications and Presentations

Purpose: Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin-spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established.

Methods: In this study, acute experimental mildly noxious stimuli were applied …

Magnetic Nanoformulations For Prostate Cancer, Pallabita Chowdhury, Allison M. Roberts, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications and Presentations

Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement characteristics, MNPs have been encouraged for pre-clinical studies and human use. As a theranostic platform development, MNPs need to balance both delivery and imaging aspects. Thus, this review provides significant insight and advances in the theranostic role of MNPs through the documentation of unique magnetic nanoparticles used in prostate cancer, their interaction with prostate cancer cells, in vivo …

The Heritability Of Multi-Modal Connectivity In Human Brain Activity, Giles L. Colclough, Stephen M. Smith, Thomas E. Nichols, Anderson M. Winkler, Stamatios N. Sotiropoulos, Matthew F. Glasser, David C. Van Essen, Mark W. Woolrich

School of Medicine Publications and Presentations

Patterns of intrinsic human brain activity exhibit a profile of functional connectivity that is associated with behaviour and cognitive performance, and deteriorates with disease. This paper investigates the relative importance of genetic factors and the common environment between twins in determining this functional connectivity profile. Using functional magnetic resonance imaging (fMRI) on 820 subjects from the Human Connectome Project, and magnetoencephalographic (MEG) recordings from a subset, the heritability of connectivity among 39 cortical regions was estimated. On average over all connections, genes account for about 15% of the observed variance in fMRI connectivity (and about 10% in alpha-band and 20% …

Ovarian Hormones Modify Anxiety Behavior And Glucocorticoid Receptors After Chronic Social Isolation Stress, Dinah L. Ramos-Ortolaza, Raura J. Doreste-Mendez, John K. Alvarado-Torres, Annelyn Torres-Reveron

School of Medicine Publications and Presentations

Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats. We assigned rats to either isolated or paired housing for 8 weeks. To assess anxiety and depressive-like behaviors, we …

Heritability And Genetic Correlation Between Gerd Symptoms Severity, Metabolic Syndrome, And Inflammation Markers In Families Living In Mexico City, Arturo Reding-Bernal, Valentin Sánchez-Pedraza, Hortensia Moreno-Macías, Sergio Sobrino-Cossio, María Elizabeth Tejero-Barrera, Ana Isabel Burguete-García, Mireya Leon-Hernandez, María Fabiola Serratos-Canales, Ravi Duggirala, Juan Carlos Lopez Alvarenga

School of Medicine Publications and Presentations

Objective: The aim of this study was to estimate the heritability (h2) and genetic correlation (ρG) between GERD symptoms severity, metabolic syndrome components, and inflammation markers in Mexican families.

Methods: Cross-sectional study which included 32 extended families resident in Mexico City. GERD symptoms severity was assessed by the ReQuest in Practice questionnaire. Heritability and genetic correlation were determined using the Sequential Oligogenic Linkage Analysis Routines software.

Results: 585 subjects were included, the mean age was 42 (±16.7) years, 57% were women. The heritability of the severity of some GERD symptoms was h2 = 0.27, 0.27, 0.37, and 0.34 (p-value <1.0x10-5) for acidity complaints, lower abdominal complaints, sleep disturbances, and total ReQuest score, respectively. Heritability of metabolic syndrome components ranged from 0.40 for fasting plasma glucose to 0.61 for body mass index and diabetes mellitus. The heritability for fibrinogen and C-reactive protein was 0.64 and 0.38, respectively. Statistically significant genetic correlations were found between acidity complaints and fasting plasma glucose (ρG = 0.40); sleep disturbances and fasting plasma glucose (ρG = 0.36); acidity complaints and diabetes mellitus (ρG = 0.49) and between total ReQuest score and fasting plasma glucose (ρG = 0.43). The rest of metabolic syndrome components did not correlate with GERD symptoms.

Conclusion: …