Medicine and Health Sciences Commons^™

A Positive-Negative Mode Of Population Covariation Links Brain Connectivity, Demographics And Behavior, Stephen M. Smith, Thomas E. Nichols, Diego Vidaurre, Anderson M. Winkler, Timothy E J Behrens, Matthew F. Glasser, Kamil Ugurbil, Deanna M. Barch, David C. Van Essen, Karla L. Miller

School of Medicine Publications

We investigated the relationship between individual subjects' functional connectomes and 280 behavioral and demographic measures in a single holistic multivariate analysis relating imaging to non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.

Novel Loci Associated With Usual Sleep Duration: The Charge Consortium Genome-Wide Association Study, D. J. Gottlieb, K. Hek, T. H. Chen, N. F. Watson, G. Eiriksdottir, E. M. Byrne, M. Cornelis, S. C. Warby, S. Bandinelli, John Blangero

School of Medicine Publications

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10 -4). The strongest …

The Transcriptional Landscape Of Age In Human Peripheral Blood, Marjolein J. Peters, Roby Joehanes, Luke C. Pilling, Claudia Schurmann, Karen N. Conneely, Harald H. H. Goring, Joanne E. Curran, Sarah Williams-Blangero, John Blangero

School of Medicine Publications

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of …

A Phenomic Scan Of The Norfolk Island Genetic Isolate Identifies A Major Pleiotropic Effect Locus Associated With Metabolic And Renal Disorder Markers, Miles C. Benton, Rodney A. Lea, Donia Macartney-Coxson, Michelle Hanna, David A. Eccles, Melanie A. Carless, Claire Bellis, Harald H. H. Goring, Joanne E. Curran, John Blangero

School of Medicine Publications

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

The Influence Of Age And Sex On Genetic Associations With Adult Body Size And Shape: A Large-Scale Genome-Wide Interaction Study, Thomas W. Winkler, Anne E. Justice, Mariaelisa Graff, Llilda Barata, Mary F. Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, John Blangero

School of Medicine Publications

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to …

Cissus Quadrangularis Linn. Stem Ethanolic Extract Liberates Reactive Oxygen Species And Induces Mitochondria Mediated Apoptosis In Kb Cells, Saba Sheikh, Sahabjada Siddiqui, Anupam Dhasmana, Ejazul Haque, Mohammed Kamil, Mohtashim Lohani, Mohammad Arshad, Snober Shabnam Mir

School of Medicine Publications

Background: Cissus quadrangularis Linn. (CQ) commonly known as Hadjod (Family: Vitaceae) is usually distributed in India and Sri Lanka and contains several bioactive compounds responsible for various metabolic and physiologic effects.

Objective: In this study, the biological effects of CQ ethanolic extract were evaluated by in vitro and supported by in silico analysis on KB oral epidermoid cancer cell line.

Materials and methods: Anti-cancer potential of ethanolic extract of CQ stem against KB oral epidermoid cancer cells was evaluated in terms of morphological analysis, nuclei staining, liberation of reactive oxygen species (ROS), cell cycle arrest, mitochondrial membrane potential (MMP) and …

Successes, Challenges And Needs Regarding Rural Health Medical Education In Continental Central America: A Literature Review And Narrative Synthesis, Maria C. Colon-Gonzalez, F. El Rayess, S. Guevara, G. Anandarajah

School of Medicine Publications

Introduction: Central American countries, like many others, face a shortage of rural health physicians. Most medical schools in this region are located in urban areas and focus on tertiary care training rather than on community health or primary care, which are better suited for rural practice. However, many countries require young physicians to do community service in rural communities to address healthcare provider shortages. This study aimed to: (a) synthesize what is known about the current state of medical education preparing physicians for rural practice in this region, and (b) identify common needs, challenges and opportunities for improving medical education …

'Mutiny On The Bounty': The Genetic History Of Norfolk Island Reveals Extreme Gender-Biased Admixture, Miles C. Benton, Shani Stuart, Claire Bellis, Donia Macartney-Coxson, David Eccles, Joanne E. Curran, Geoff Chambers, John Blangero, Rod A. Lea, L. R. Griffiths

School of Medicine Publications

Background

The Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The ‘Mutiny on the Bounty’ has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of …

Metabolites As Novel Biomarkers For Childhood Obesity-Related Traits In Mexican-American Children, V. S. Farook, L. Reddivari, G. Chittoor, S. Puppala, Rector Arya, S. P. Fowler, Joanne E. Curran, John Blangero, Ravi Duggirala

School of Medicine Publications

Background/Objectives Although newer approaches have identified several metabolites associated with obesity, there is paucity of such information in paediatric populations, especially among Mexican-Americans (MAs) who are at high risk of obesity. Therefore, we performed a global serum metabolite screening in MA children to identify biomarkers of childhood obesity. Methods We selected 15 normal-weight, 13 overweight and 14 obese MA children (6-17 years) and performed global serum metabolite screening using ultra-performance liquid chromatography/quadruple orthogonal acceleration time of flight tandem micro mass spectrometer. Metabolite values were analysed to assess mean differences among groups using one-way analysis of variance, to test for linear …

Fatty Acids Linked To Cardiovascular Mortality Are Associated With Risk Factors, Sven O. E. Ebbesson, V. Saroja Voruganti, Paul B. Higgins, Richard R. Fabsitz, Lars O. Ebbesson, Sandra Laston, William S. Harris, John Kennish, Benjamin D. Umans, Hong Wang

School of Medicine Publications

Background. Although saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors.

Objective. We tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated …

Fast And Powerful Heritability Inference For Family-Based Neuroimaging Studies, Habib Ganjgahi, Anderson M. Winkler, David C. Glahn, John Blangero, Peter Kochunov, Thomas E. Nichols

School of Medicine Publications

Heritability estimation has become an important tool for imaging genetics studies. The large number of voxel- and vertex-wise measurements in imaging genetics studies presents a challenge both in terms of computational intensity and the need to account for elevated false positive risk because of the multiple testing problem. There is a gap in existing tools, as standard neuroimaging software cannot estimate heritability, and yet standard quantitative genetics tools cannot provide essential neuroimaging inferences, like family-wise error corrected voxel-wise or cluster-wise P-values. Moreover, available heritability tools rely on P-values that can be inaccurate with usual parametric inference methods. In this work …

Alterations In Activation, Cytotoxic Capacity And Trafficking Profile Of Peripheral Cd8 T Cells In Young Adult Binge Drinkers, José Luis Zaldivar Fujigaki, América Guadalupe Arroyo Valerio, Juan Carlos Lopez Alvarenga, Esperanza Gabriela Gutiérrez Reyes, David Kershenobich, Joselin Hernández Ruiz

School of Medicine Publications

Background: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity.

Aim: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern.

Methods: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their …

Striatal Activity And Reduced White Matter Increase Frontal Activity In Youths With Family Histories Of Alcohol And Other Substance-Use Disorders Performing A Go/No-Go Task, Ashley Acheson, Malle A. Tagamets, Anderson M. Winkler, Laura M. Rowland, Charles W. Mathias, Susan N. Wright, L. Elliot Hong, Peter Kochunov, Donald M. Dougherty

School of Medicine Publications

Introduction: Youths with a family history of alcohol and other drug use disorders (FH+) are at greater risk of developing substance-use disorders relative to those with no such family histories (FH-). We previously reported that FH+ youths have elevated activity in the supplementary motor area (SMA) and dorsal striatum while performing go/no-go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in FH+ youths, which may be an important contributor to their elevated risk.

Methods: In this study, we used structural equation modeling (SEM) …

In Silico Molecular Docking Analysis To Predict The Role Of Metal Ions In The Function Of Drug Targeted Proteins, S. M. A. Shahid, Qazi M. S. Jamal, J. M. Arif, Fahad M. Al-Khodairy, Anupam Dhasmana, Mohtashim Lohani

School of Medicine Publications

Metal ions are required for many critical functions in living systems. Scarcity of some metal ions can lead to disease. A characteristic of metals is that they easily lose electrons from the familiar elemental or metallic state to form positively charged ions which tend to be soluble in biological fluids. Role of zinc, calcium and copper ions in the catalytic mechanism of drug targeted proteins such as Farnesyltransferase, Neuraminidase and Thioredoxin are analyzed using molecular docking, respectively. The docking results show that inhibitors have low Binding, docking and internal energies with proteins in the presence of Zn, Ca and Cu …

Anticancer Activity Of Cissus Quadrangularis: An In Vitro 2d Model Based Study, Saba Sheikh, Anupam Dhasmana, Sahabjada Siddiqui, Ejazul Haque

School of Medicine Publications

Cissus quadrangularis (CQ) is a perennial rambling shrub of the grape family commonly known as “Hadjora” (in Hindi) probably native to India or Sri Lanka. It is one of the valuable medicines in the Indian Traditional Systems of Medicine because of the presence of several bioactive compounds. However, in the present study we have checked its anticancer activity along with its safety profile on normal skin cells. Apart from this we have generated the spheroid HeLa culture in vitro model for analyzing the CQ extract response on the growth of HeLa tumoroid. From the present findings we have observed that …

Sequencing Strategies And Characterization Of 721 Vervet Monkey Genomes For Future Genetic Analyses Of Medically Relevant Traits, Yu S. Huang, Vasily Ramensky, Susan K. Service, Anna J. Jasinska, Yoon Jung, Oi-Wa Choi, Rita M. Cantor, Thomas D. Dyer, John Blangero

School of Medicine Publications

Background

We report here the first genome-wide high-resolution polymorphism resource for non-human primate (NHP) association and linkage studies, constructed for the Caribbean-origin vervet monkey, or African green monkey (Chlorocebus aethiops sabaeus), one of the most widely used NHPs in biomedical research. We generated this resource by whole genome sequencing (WGS) of monkeys from the Vervet Research Colony (VRC), an NIH-supported research resource for which extensive phenotypic data are available.

Results

We identified genome-wide single nucleotide polymorphisms (SNPs) by WGS of 721 members of an extended pedigree from the VRC. From high-depth WGS data we identified more than 4 …

Does Maternal Asthma Contribute To Racial/Ethnic Disparities In Obstetric And Neonatal Complications?, Katrina F. Flores, Candace Robledo, Beom Seuk Hwang, Kira Leishear, Katherine Grantz, Pauline Mendola

School of Medicine Publications

Purpose

Examine whether maternal asthma contributes to racial/ethnic differences in obstetric and neonatal complications.

Methods

Data on White (n=110,603), Black (n=50,284) and Hispanic (n=38,831) singleton deliveries came from the Consortium on Safe Labor. Multi-level logistic regression models, with an interaction term for asthma and race/ethnicity, estimated within-group adjusted odds ratios (aOR) for gestational diabetes, gestational hypertension, preeclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, NICU admissions, small for gestational age (SGA), apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia and hyperbilirubinemia after adjustment for clinical and demographic confounders. Non-asthmatics of the same racial/ethnic group were …

Plumbagin Inhibits Prostate Carcinogenesis In Intact And Castrated Pten Knockout Mice Via Targeting Pkcε, Stat3, And Epithelial-To-Mesenchymal Transition Markers, Bilal B. Hafeez, Joseph W. Fischer, Ashok Singh, Weixiong Zhong, Ala Mustafa, Louise Meske, Mohammad Ozair Sheikhani, Ajit K. Verma

School of Medicine Publications

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 …

Heritability Of Fractional Anisotropy In Human White Matter: A Comparison Of Human Connectome Project And Enigma-Dti Data, Peter Kochunov, Neda Jahanshad, Daniel Marcus, Anderson M. Winkler, Laura Almasy, Joanne E. Curran, Ravi Duggirala, Peter T. Fox, Rene L. Olvera, John Blangero

School of Medicine Publications

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA …

Urinary Phthalate Metabolite Concentrations And Blood Glucose Levels During Pregnancy, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Antonia M. Calafat, Hélène Carabin, Linda Cowan, Jean R. Goodman

School of Medicine Publications

Purpose: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM).

Methods: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine …

Common Genetic Variants Influence Human Subcortical Brain Structures, Derrek P. Hibar, Jason L. Stein, Miguel E. Renteria, Alejandro Arias-Vasquez, John Blangero, Anderson M. Winkler, Joanne E. Curran, Thomas D. Dyer, Peter T. Fox, Ravi Duggirala

School of Medicine Publications

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence …

Transcriptomic Identification Of Adh1b As A Novel Candidate Gene For Obesity And Insulin Resistance In Human Adipose Tissue In Mexican Americans From The Veterans Administration Genetic Epidemiology Study (Vages), Deidre A. Winnier, Marcel Fourcaudot, Luke Norton, Muhammad A. Abdul-Ghani, Shirley L. Hu, Thomas D. Dyer, Joanne E. Curran, John Blangero, Ravi Duggirala, Harald H. H. Goring

School of Medicine Publications

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data …

Influence Of Depression, Anxiety And Stress On Cognitive Performance In Community-Dwelling Older Adults Living In Rural Ecuador: Results Of The Atahualpa Project, Oscar H. Del Brutto, Robertino M. Mera, Victor J. Del Brutto, Gladys Maestre, Hannah Gardener, Mauricio Zambrano, Clinton B. Wright

School of Medicine Publications

Aim:

To assess the relationship between cognitive status and self-reported symptoms of depression, anxiety and stress of older adults living in an underserved rural South American population.

Methods:

Community-dwelling Atahualpa residents aged ≥60 years were identified during a door-to-door census, and evaluated with the Depression Anxiety Stress Scale-21 (DASS-21) and the Montreal Cognitive Assessment (MoCA). We explored whether positivity in each of the DASS-21 axes was related to total and domain-specific MoCA performance after adjustment for age, sex and education.

Results:

A total of 280 persons (59% women; mean age, mean age 70 ± 8 years) were included. Based on …

Interaction Pattern For The Complex Of B-Dnafullerene Compounds With A Set Of Known Replication Proteins Using Docking Study, Sumbul Firdaus, Anupam Dhasmana, Vandana Srivastava, Tasneem Bano, Afreen Fatima, Qazi Mohammad Sajid Jamal, Roshan Jahan, Gulshan Wadhwad, Mohtashim Lohani

School of Medicine Publications

Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications which has opened wide venues for possible human exposure to various fullerene types. Therefore, in depth knowledge of how fullerene may interfere with various cellular processes becomes quite imperative. The present study was designed to investigate how the presence of fullerene affect the binding of DNA with different enzymes involved in replication process. Different fullerenes were first docked with DNA and then binding scores of different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50 once docked with DNA, reduced the binding score of …

Non-Crossover Gene Conversions Show Strong Gc Bias And Unexpected Clustering In Humans, Amy L. Williams, Giulio Genovese, Thomas D. Dyer, Nicolas Altemose, Katherine Truax, Goo Jun, Nick Patterson, Joanne E. Curran, Ravi Duggirala, John Blangero

School of Medicine Publications

Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by NCO, of which 50/52 were confirmed in sequence data. Overlap with double strand break (DSB) hotspots indicates that most of the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.9×10-6/bp/generation, consistent with sperm-typing studies, and infer that tract lengths span at least …

Evaluation Of Neurotrophic Tyrosine Receptor Kinase 2 (Ntrk2) As A Positional Candidate Gene For Variation In Estimated Glomerular Filtration Rate (Egfr) In Mexican American Participants Of San Antonio Family Heart Study, Farook Thameem, V. Saroja Voruganti, John Blangero, Anthony G. Comuzzie, Hanna E. Abboud

School of Medicine Publications

Background

The estimated glomerular filtration rate (eGFR) is a well-known measure of kidney function and is commonly used for the diagnosis and management of patients with chronic kidney disease. The inter-individual variation in eGFR has significant genetic component. However, the identification of underlying genetic susceptibility variants has been challenging. In an attempt to identify and characterize susceptibility genetic variant(s) we previously identified the strongest evidence for linkage of eGFR occurring on chromosome 9q21 in the Mexican American participants of San Antonio Family Heart Study (SAFHS). The objective of the present study was to examine whether the common genetic variants in …

Association Of Insurance Status With Health Outcomes Following Traumatic Injury: Statewide Multicenter Analysis, Vatsal Chikani, Maureen Brophy, Anne Vossbrink, Khaleel Hussaini, Christopher Salvino, Jeffrey Skubic, Rogelio Martinez

School of Medicine Publications

Introduction: Recognizing disparities in definitive care for traumatic injuries created by insurance status may help reduce the higher risk of trauma-related mortality in this population. Our objective was to understand the relationship between patients' insurance status and trauma outcomes.

Methods: We collected data on all patients involved in traumatic injury from eight Level I and 15 Level IV trauma centers, and four non-designated hospitals through Arizona State Trauma Registry between January 1, 2008 and December 31, 2011. Of 109,497 records queried, we excluded 29,062 (26.5%) due to missing data on primary payer, sex, race, zip code of residence, injury severity …

Whole-Genome Sequencing To Understand The Genetic Architecture Of Common Gene Expression And Biomarker Phenotypes, Andrew R. Wood, Marcus A. Tuke, Mike Nalls, Dena Hernandez, J. Raphael Gibbs, Haoxiang Lin, Christopher S. Xu, Marcio Almeida, John Blangero, Joanne E. Curran, Harald H. H. Goring

School of Medicine Publications

Initial results from sequencing studies suggest that there are relatively few low-frequency (<5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency–large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant–common phenotype associations—11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (<5%), respectively, low frequency–large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P < 1 × 10⁻⁰⁶ (false discovery rate ∼5%)] and one of eight biomarker associations at P < 8 × 10⁻¹⁰. Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can …

Interaction Pattern Of Fullerene Family With Different Forms Of Dna, Sumbul Firdaus, Mohtashim Lohani, Anupam Dhasmana, Mohd. Haneef

School of Medicine Publications

Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications. In this study fullerenes (C20 to C180) were interacted with different forms of DNA i.e. A, B and Z-forms. And no such change in the binding score was observed with the change in the sequence of DNA. In fact, binding score increases with the increase in the molecular weight of the fullerene while interacting with A & B-form of DNA but Z-form of DNA shows no regular pattern of binding. Number of interacting base pairs increases as the molecular size of fullerene increases. And the groove …

Genetic Influences On Response To Novel Objects And Dimensions Of Personality In Papio Baboons, Zachary Johnson, Linda Brent, Juan Carlos Lopez Alvarenga, Anthony G. Comuzzie, Wendy Shelledy, Stephanie Ramirez, Laura Cox, Michael C. Mahaney, Yung-Yu Huang, John Mann

School of Medicine Publications

Behavioral variation within and between populations and species of the genus Papio has been studied extensively, but little is known about the genetic causes of individual- or population-level differences. This study investigates the influence of genetic variation on personality (sometimes referred to as temperament) in baboons and identifies a candidate gene partially responsible for the variation in that phenotype. To accomplish these goals, we examined individual variation in response to both novel objects and an apparent novel social partner (using a mirror test) among pedigreed baboons (n = 578) from the Southwest National Primate Research Center. We investigated the frequency …