46 results on '"Morgan, Thomas M."'
Search Results
2. Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome
- Author
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Abelson, Jesse F., Kwan, Kenneth Y., O'Roak, Brian J., Baek, Danielle Y., Stillman, Althea A., Morgan, Thomas M., Mathews, Carol A., Pauls, David L., Rašin, Mladen-Roko, Gunel, Murat, Davis, Nicole R., Ercan-Sencicek, A. Gulhan, Guez, Danielle H., Spertus, John A., Leckman, James F., Dure, Leon S., Kurlan, Roger, Singer, Harvey S., Gilbert, Donald L., Farhi, Anita, Louvi, Angeliki, Lifton, Richard P., Šestan, Nenad, and State, Matthew W.
- Published
- 2005
3. Epigenetic Abnormalities Associated with a Chromosome 18(q21-q22) Inversion and a Gilles de la Tourette Syndrome Phenotype
- Author
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State, Matthew W., Greally, John M., Cuker, Adam, Bowers, Peter N., Henegariu, Octavian, Morgan, Thomas M., Gunel, Murat, DiLuna, Michael, King, Robert A., Nelson, Carol, Donovan, Abigail, Anderson, George M., Leckman, James F., Hawkins, Trevor, Pauls, David L., Lifton, Richard P., and Ward, David C.
- Published
- 2003
4. Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes
- Author
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Hufnagel, Robert B, Arno, Gavin, Hein, Nichole D, Hersheson, Joshua, Prasad, Megana, Anderson, Yvonne, Krueger, Laura A, Gregory, Louise C, Stoetzel, Corinne, Jaworek, Thomas J, Hull, Sarah, Li, Abi, Plagnol, Vincent, Willen, Christi M, Morgan, Thomas M, Prows, Cynthia A, Hegde, Rashmi S, Riazuddin, Saima, Grabowski, Gregory A, Richardson, Rudy J, Dieterich, Klaus, Huang, Taosheng, Revesz, Tamas, Martinez-Barbera, J P, Sisk, Robert A, Jefferies, Craig, Houlden, Henry, Dattani, Mehul T, Fink, John K, Dollfus, Helene, Moore, Anthony T, and Ahmed, Zubair M
- Published
- 2015
- Full Text
- View/download PDF
5. Correlation of Heart Rate and Cardiac Dysfunction in Duchenne Muscular Dystrophy
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Thomas, Tamara O., Morgan, Thomas M., Burnette, William B., and Markham, Larry W.
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- 2012
- Full Text
- View/download PDF
6. L-histidine decarboxylase and Tourette's syndrome
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Ercan-Sencicek, A. Gulhan, Stillman, Althea A., Ghosh, Ananda K., Bilguvar, Kaya, O'Roak, Brian J., Mason, Christopher E., Abbott, Thomas, Gupta, Abha, King, Robert A., Pauls, David L., Tischfield, Jay A., Heiman, Gary A., Singer, Harvey S., Gilbert, Donald L., Hoekstra, Pieter J., Morgan, Thomas M., Loring, Erin, Yasuno, Katsuhito, Fernandez, Thomas, Sanders, Stephan, Louvi, Angeliki, Cho, Judy H., Mane, Shrikant, Colangelo, Christopher M., Biederer, Thomas, Lifton, Richard P., Gunel, Murat, and State, Matthew W.
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Decarboxylases -- Genetic aspects ,Gene mutations -- Analysis ,Histidine -- Research ,Tourette's syndrome -- Genetic aspects ,Tourette's syndrome -- Diagnosis ,Tourette's syndrome -- Care and treatment - Abstract
An analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase and Tourette's syndrome, the rate-limiting enzyme in histamine biosynthesis is described. The study findings along with the published data from model system provide insight into the role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.
- Published
- 2010
7. Brief Report: Risk of Adverse Fetal Outcomes Associated With Immunosuppressive Medications for Chronic Immune-Mediated Diseases in Pregnancy
- Author
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Cooper, William O., Cheetham, Craig T., Li, De-Kun, Stein, Michael C., Callahan, Todd S., Morgan, Thomas M., Shintani, Ayumi K., Chen, Ning, Griffin, Marie R., and Ray, Wayne A.
- Published
- 2014
- Full Text
- View/download PDF
8. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders
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Bakkaloglu, Betul, O'Roak, Brian J., Louvi, Angeliki, Gupta, Abha R., Abelson, Jesse F., Morgan, Thomas M., Chawarska, Katarzyna, Klin, Ami, Ercan-Sencicek, A. Gulhan, Stillman, Althea A., Tanriover, Gamze, Abrahams, Brett S., Duvall, Jackie A., Robbins, Elissa M., Geshwind, Daniel H., Biederer, Thomas, Gunel, Murat, Lifton, Richard P., and State, Matthew W.
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Human cytogenetics -- Research ,Autistic children -- Genetic aspects ,Autistic children -- Research ,Amino acid sequence -- Research ,Biological sciences - Abstract
A de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with congitive and social delay is identified. It is suggested that rare variants contribute to the pathophysiology of autism spectrum disorders (ASD).
- Published
- 2008
9. Epigenetic abnormalities associated with a chromosome 18(q21-q22)inversion and a Gilles de la Tourette syndrome phenotype
- Author
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State, Matthew W., Greally, John M., Cuker, Adam, Bowers, Peter N., Henegariu, Octavian, Morgan, Thomas M., Gunel, Murat, DiLuna, Michael, King, Robert A., Nelson, Carol, Donovan, Abigail, Anderson, George M., Leckman, James F., Hawkins, Trevor, Pauls, David L., Lifton, Richard P., and Ward, David C.
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Extrapyramidal disorders -- Genetic aspects ,Science and technology - Abstract
Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dysregulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts.
- Published
- 2003
10. Mouse models of patent ductus arteriosus (PDA) and their relevance for human PDA.
- Author
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Yarboro, Michael T., Gopal, Srirupa H., Su, Rachel L., Morgan, Thomas M., and Reese, Jeff
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DUCTUS arteriosus ,PATENT ductus arteriosus ,LABORATORY mice ,HUMAN biology ,PREMATURE infants ,CONGENITAL heart disease - Abstract
The ductus arteriosus (DA) is a unique fetal vascular shunt, which allows blood to bypass the developing lungs in utero. After birth, changes in complex signaling pathways lead to constriction and permanent closure of the DA. The persistent patency of the DA (PDA) is a common disorder in preterm infants, yet the underlying causes of PDA are not fully defined. Although limits on the availability of human DA tissues prevent comprehensive studies on the mechanisms of DA function, mouse models have been developed that reveal critical pathways in DA regulation. Over 20 different transgenic models of PDA in mice have been described, with implications for human DA biology. Similarly, we enumerate 224 human single‐gene syndromes that are associated with PDA, including a small subset that consistently feature PDA as a prominent phenotype. Comparison and functional analyses of these genes provide insight into DA development and identify key regulatory pathways that may serve as potential therapeutic targets for the management of PDA. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Better by the Pound: The Genetics of Birth Weight
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McElroy, Jude J., Muglia, Louis J., and Morgan, Thomas M.
- Published
- 2012
- Full Text
- View/download PDF
12. National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving Health
- Author
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Berg, Alfred O., Baird, Macaran A., Botkin, Jeffrey R., Driscoll, Deborah A., Fishman, Paul A., Guarino, Peter D., Hiatt, Robert A., Jarvik, Gail P., Millon-Underwood, Sandra, Morgan, Thomas M., Mulvihill, John J., Pollin, Toni I., Schimmel, Selma R., Stefanek, Michael Edward, Vollmer, William M., and Williams, Janet K.
- Published
- 2009
13. Liver Transplantation in Children with Urea Cycle Disorders: The Importance of Minimizing Waiting Time.
- Author
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Ziogas, Ioannis A., Wu, W. Kelly, Matsuoka, Lea K., Pai, Anita K., Hafberg, Einar T., Gillis, Lynette A., Morgan, Thomas M., and Alexopoulos, Sophoclis P.
- Published
- 2021
- Full Text
- View/download PDF
14. Validity of Reported Genetic Risk Factors for Acute Coronary Syndrome
- Author
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Morgan, Thomas M., Krumholz, Harlan M., Lifton, Richard P., and Spertus, John A.
- Published
- 2007
15. Nonvalidation of Reported Genetic Risk Factors for Acute Coronary Syndrome in a Large-Scale Replication Study
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Morgan, Thomas M., Krumholz, Harlan M., Lifton, Richard P., and Spertus, John A.
- Published
- 2007
16. Reporting of model validation procedures in human studies of genetic interactions
- Author
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Coffey, Christopher S, Hebert, Patricia R, Krumholz, Harlan M, Morgan, Thomas M, Williams, Scott M, and Moore, Jason H
- Published
- 2004
- Full Text
- View/download PDF
17. Maternal Smoking and Congenital Birth Defects
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Morgan, Thomas M.
- Published
- 2002
18. The Economic Impact of Wasted Prescription Medication in an Outpatient Population of Older Adults
- Author
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Morgan, Thomas M.
- Published
- 2001
19. Siblings, Day-Care Attendance, and the Risk of Asthma and Wheezing
- Author
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Morgan, Thomas M.
- Published
- 2000
20. Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome
- Author
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Winkelmann Bernhard R, März Winfried, Kleber Marcus E, Quyyumi Arshed A, Waddy Salina P, Eapen Danny J, Patel Riyaz S, Patel Yesha, Hazen Stanley L, Allayee Hooman, Jones Philip, Cresci Sharon, Morgan Thomas M, House John A, Boehm Bernhard O, Krumholz Harlan M, and Spertus John A
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. Methods We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. Results After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). Conclusions We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.
- Published
- 2011
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- View/download PDF
21. Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype
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Wise Carol A, Dobbs Matthew B, Gurnett Christina A, McGregor Tracy L, Morcuende Jose A, Morgan Thomas M, Menon Ramkumar, and Muglia Louis J
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Although adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. Work in model organisms, including zebrafish, chickens, and mice, has implicated the lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis. Methods This was a case-control genetic association study. A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were tested for association with adolescent idiopathic scoliosis by logistic regression with a two degree of freedom genotypic model and gender as a covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an independent replication cohort of 400 cases and 506 controls. Results No evidence for significant association was found between coding or tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic scoliosis. Conclusions Despite suggestive evidence in model organisms, common variants and known coding SNPs in the five human lysyl oxidase genes do not confer increased genotypic risk for adolescent idiopathic scoliosis. The above methodology does not address rare variants or individually private mutations in these genes, and future research may focus on this area.
- Published
- 2011
- Full Text
- View/download PDF
22. Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome
- Author
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Krumholz Harlan M, Kassebaum Bethany, Lyons Patrick, Xiao Lan, Morgan Thomas M, and Spertus John A
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown. Methods We examined the association of putative genetic risk factors with 3-year post-ACS mortality in 811 ACS survivors at university-affiliated hospitals in Kansas City, Missouri. Through a systematic literature search, we first identified genetic variants reported as susceptibility factors for atherosclerosis or ACS. Restricting our analysis to whites, so as to avoid confounding from racial admixture, we genotyped ACS cases for 89 genetic variants in 72 genes, and performed individual Kaplan-Meier survival analyses. We then performed Cox regression to create multivariate risk prediction models that further minimized potential confounding. Results Of 89 variants tested, 16 were potentially associated with mortality (P < 0.1 for all), of which 6 were significantly associated (P < 0.05) with mortality following ACS. While these findings are not more than what would be expected by chance (P = 0.28), even after Bonferroni correction and adjustment for traditional cardiac risk factors, the IRS1 972Arg variant association (P = 0.001) retained borderline statistical significance (P < 0.1). Conclusion With the possible exception of IRS1, we conclude that multiple candidate genes were not associated with post-ACS mortality in our patient cohort. Because of power limitations, the 16 gene variants with P values < 0.1 may warrant further study. Our data do not support the hypothesis that the remaining 73 genes have substantial, clinically significant association with mortality after an ACS.
- Published
- 2008
- Full Text
- View/download PDF
23. Rules for the Design of Water Supply Systems, Ventura County, Calif.
- Author
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Morgan, Thomas M.
- Published
- 1962
24. Genomic Screening: The Mutation and the Mustard Seed.
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Morgan, Thomas M.
- Subjects
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GENOMICS , *BIOETHICS , *GENETIC mutation , *HUMAN genome - Abstract
The author discusses bioethics and argues that the pace of genomic screening is too rapid and without proper consideration for the impact on the global clinical ecosystem.
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- 2018
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25. A balanced t(10;15) translocation in a male patient with developmental language disorder
- Author
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Ercan-Sencicek, A. Gulhan, Davis Wright, Nicole R., Sanders, Stephan J., Oakman, Nicole, Valdes, Lianna, Bakkaloglu, Betul, Doyle, Niamh, Yrigollen, Carolyn M., Morgan, Thomas M., and Grigorenko, Elena L.
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- 2012
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26. Prader-Willi Syndrome: Development and Manifestations
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Krumholz, Samuel K. and Morgan, Thomas M.
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Prader-Willi Syndrome: Development and Manifestations (Book) -- Book reviews ,Books -- Book reviews ,Family and marriage ,Psychology and mental health - Published
- 2005
27. The education and medical practice of Dr. James McCune Smith (1813-1865), first black American to hold a medical degree
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Morgan, Thomas M.
- Subjects
Black or African American ,Human Rights ,Social Problems ,Physicians ,Humans ,History, 20th Century ,United States ,Research Article - Abstract
James McCune Smith (1813-1865)--first black American to obtain a medical degree, prominent abolitionist and suffragist, compassionate physician, prolific writer, and public intellectual--has been relatively neglected by historians of medicine. No biography of Smith exists to this day, though he has been the subject of several essays. Born, in his own words, "the son of a self-emancipated bond-woman," and denied admission to colleges in the United States, his native land, Smith earned medical, master's, and baccalaureate degrees at Glasgow University in Scotland. On his return to New York City in 1837, Smith became the first black physician to publish articles in US medical journals. Smith was broadly involved in the anti-slavery and suffrage movements, contributing to and editing abolitionist newspapers and serving as an officer of many organizations for the improvement of social conditions in the black community. In his scientific writings Smith debunked the racial theories in Thomas Jefferson's Notes on the State of Virginia, refuted phrenology and homeopathy, and responded with a forceful statistical critique to the racially biased US Census of 1840. Frederick Douglass, Gerrit Smith, and John Brown personally collaborated with James McCune Smith in the fight for black freedom. As the learned physician-scholar of the abolition movement, Smith was instrumental in making the overthrow of slavery credible and successful.
- Published
- 2003
28. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans.
- Author
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Ercan-Sencicek, A Gulhan, Jambi, Samira, Franjic, Daniel, Nishimura, Sayoko, Li, Mingfeng, El-Fishawy, Paul, Morgan, Thomas M, Sanders, Stephan J, Bilguvar, Kaya, Suri, Mohnish, Johnson, Michele H, Gupta, Abha R, Yuksel, Zafer, Mane, Shrikant, Grigorenko, Elena, Picciotto, Marina, Alberts, Arthur S, Gunel, Murat, Šestan, Nenad, and State, Matthew W
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MICROCEPHALY ,GENETIC research ,ACTIN ,PROTEIN genetics ,BRAIN chemistry ,CELL adhesion ,GENETICS - Abstract
The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
29. Genetic Risk Score Does Not Correlate with Body Mass Index of Latina Women in a Clinical Trial.
- Author
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Coenen, Kimberly R., Karp, Sharon M., Gesell, Sabina B., Dietrich, Mary S., Morgan, Thomas M., and Barkin, Shari L.
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OBESITY ,HISPANIC American women ,GENETICS ,BODY mass index ,CLINICAL trials - Abstract
Obesity disproportionately affects Latina women. Common genetic variants are convincingly associated with body mass index (BMI) and may be used to create genetic risk scores (GRS) for obesity that could define genetically influenced forms of obesity and alter response to clinical trial interventions. The objective of this study was (1) to identify the frequency and effect size of common obesity genetic variants in Latina women; (2) to determine the clinical utility of a GRS for obesity with Latina women participating in a community-based clinical trial. DNA from 85 Latina women was genotyped for eight genetic variants previously associated with BMI in Caucasians, but not yet assessed in Latina populations. The main outcome measure was the correlation of GRS (sum of eight risk alleles) with BMI, waist circumference, and percent body fat. A majority (83%) of participants had a BMI ≥25. Frequency of loci near FTO, MC4R, and GNPDA2 were lower in Latinas than Caucasians. Association of each locus with BMI was lower in Latinas compared to Caucasians with no significant correlations with BMI. We conclude that an eight locus GRS has no clinical utility for explaining obesity or predicting response to intervention in Latina women participating in a clinical trial. Clin Trans Sci 2011; Volume 4: 323-327 [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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30. Analyzing exotic instructions for a retargetable code generator.
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Morgan, Thomas M. and Rowe, Lawrence A.
- Published
- 1982
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31. Variation in recovery: Role of gender on outcomes of young AMI patients (VIRGO) study design.
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Lichtman, Judith H, Lorenze, Nancy P, D'Onofrio, Gail, Spertus, John A, Lindau, Stacy T, Morgan, Thomas M, Herrin, Jeph, Bueno, Héctor, Mattera, Jennifer A, Ridker, Paul M, and Krumholz, Harlan M
- Subjects
MYOCARDIAL infarction diagnosis ,MYOCARDIAL infarction-related mortality ,MYOCARDIAL infarction treatment ,COMPARATIVE studies ,EPIDEMIOLOGICAL research ,HOSPITAL care ,RESEARCH methodology ,MEDICAL cooperation ,MYOCARDIAL infarction ,PROGNOSIS ,RESEARCH ,RESEARCH funding ,SEX distribution ,SURVIVAL analysis (Biometry) ,EVALUATION research ,RELATIVE medical risk ,TREATMENT effectiveness - Abstract
Background: Among individuals with ischemic heart disease, young women with an acute myocardial infarction (AMI) represent an extreme phenotype associated with an excess mortality risk. Although women younger than 55 years of age account for less than 5% of hospitalized AMI events, almost 16 000 deaths are reported annually in this group, making heart disease a leading killer of young women. Despite a higher risk of mortality compared with similarly aged men, young women have been the subject of few studies.Methods and Results: Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) is a large, observational study of the presentation, treatment, and outcomes of young women and men with AMI. VIRGO will enroll 2000 women, 18 to 55 years of age, with AMI and a comparison cohort of 1000 men with AMI from more than 100 participating hospitals. The aims of the study are to determine sex differences in the distribution and prognostic importance of biological, demographic, clinical, and psychosocial risk factors; to determine whether there are sex differences in the quality of care received by young AMI patients; and to determine how these factors contribute to sex differences in outcomes (including mortality, hospitalization, and health status). Blood serum and DNA for consenting participants will be stored for future studies.Conclusions: VIRGO will seek to identify novel and prognostic factors that contribute to outcomes in this young AMI population. Results from the study will be used to develop clinically useful risk-stratification models for young AMI patients, explain sex differences in outcomes, and identify targets for intervention. [ABSTRACT FROM AUTHOR]- Published
- 2010
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32. Consanguinity Mapping of Congenital Heart Disease in a South Indian Population.
- Author
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McGregor, Tracy L., Misri, Amit, Bartlett, Jackie, Orabona, Guilherme, Friedman, Richard D., Sexton, David, Maheshwari, Sunita, and Morgan, Thomas M.
- Abstract
Background: Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents. Methodology/Principal Findings: In this linkage scan involving single nucleotide polymorphism (SNP) markers, the threshold for genome-wide statistical significance was set at the standard log-of-odds (LOD) score threshold of 3.3, corresponding to 1995:1 odds in favor of linkage. We identified a maximal single-point LOD score of 3.76 (5754:1 odds) implicating linkage of CHD with the major allele (G) of rs1055061 on chromosome 14 in the HOMEZ gene, a ubiquitously expressed transcription factor containing leucine zipper as well as zinc finger motifs. Re-sequencing of HOMEZ exons did not reveal causative mutations in Indian probands. In addition, genotyping of the linked allele (G) in 325 U.S. CHD cases revealed neither genotypic nor allele frequency differences in varied CHD cases compared to 605 non-CHD controls. Conclusions/Significance: Despite the statistical power of the consanguinity mapping approach, no single gene of major effect could be convincingly identified in a clinically heterogeneous sample of Indian CHD cases born to consanguineous parents. However, we are unable to exclude the possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD in the Indian population. Further research involving large multinational cohorts of patients with specific subtypes of CHD is needed to attempt replication of the observed linkage peak on chromosome 14. In addition, we anticipate that a targeted re-sequencing approach may complement linkage analysis in future studies of recessive mutation detection in CHD. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
33. Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome.
- Author
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Morgan, Thomas M., Lan Xiao, Lyons, Patrick, Kassebaum, Bethany, Krumholz, Harlan M., and Spertus, John A.
- Subjects
- *
GENES , *GENETICS , *MORTALITY , *CORONARY disease , *HEART diseases - Abstract
Background: Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown. Methods: We examined the association of putative genetic risk factors with 3-year post-ACS mortality in 811 ACS survivors at university-affiliated hospitals in Kansas City, Missouri. Through a systematic literature search, we first identified genetic variants reported as susceptibility factors for atherosclerosis or ACS. Restricting our analysis to whites, so as to avoid confounding from racial admixture, we genotyped ACS cases for 89 genetic variants in 72 genes, and performed individual Kaplan-Meier survival analyses. We then performed Cox regression to create multivariate risk prediction models that further minimized potential confounding. Results: Of 89 variants tested, 16 were potentially associated with mortality (P < 0.1 for all), of which 6 were significantly associated (P < 0.05) with mortality following ACS. While these findings are not more than what would be expected by chance (P = 0.28), even after Bonferroni correction and adjustment for traditional cardiac risk factors, the IRS1 972Arg variant association (P = 0.001) retained borderline statistical significance (P < 0.1). Conclusion: With the possible exception of IRS1, we conclude that multiple candidate genes were not associated with post-ACS mortality in our patient cohort. Because of power limitations, the 16 gene variants with P values < 0.1 may warrant further study. Our data do not support the hypothesis that the remaining 73 genes have substantial, clinically significant association with mortality after an ACS. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
34. X.―Ethyl-phenyl-acetylene.
- Author
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Morgan, Thomas M.
- Published
- 1876
- Full Text
- View/download PDF
35. USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder.
- Author
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Hao, Yi-Heng, Jr.Fountain, Michael D., Fon Tacer, Klementina, Xia, Fan, Bi, Weimin, Kang, Sung-Hae L., Patel, Ankita, Rosenfeld, Jill A., Le Caignec, Cédric, Isidor, Bertrand, Krantz, Ian D., Noon, Sarah E., Pfotenhauer, Jean P., Morgan, Thomas M., Moran, Rocio, Pedersen, Robert C., Saenz, Margarita S., Schaaf, Christian P., and Potts, Patrick Ryan
- Subjects
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GENETIC mutation , *NEUROBEHAVIORAL disorders , *UBIQUITIN ligases , *HOMEOSTASIS , *CELL communication , *ENDOSOMES - Abstract
Summary Endosomal protein recycling is a fundamental cellular process important for cellular homeostasis, signaling, and fate determination that is implicated in several diseases. WASH is an actin-nucleating protein essential for this process, and its activity is controlled through K63-linked ubiquitination by the MAGE-L2-TRIM27 ubiquitin ligase. Here, we show that the USP7 deubiquitinating enzyme is an integral component of the MAGE-L2-TRIM27 ligase and is essential for WASH-mediated endosomal actin assembly and protein recycling. Mechanistically, USP7 acts as a molecular rheostat to precisely fine-tune endosomal F-actin levels by counteracting TRIM27 auto-ubiquitination/degradation and preventing overactivation of WASH through directly deubiquitinating it. Importantly, we identify de novo heterozygous loss-of-function mutations of USP7 in individuals with a neurodevelopmental disorder, featuring intellectual disability and autism spectrum disorder. These results provide unanticipated insights into endosomal trafficking, illuminate the cooperativity between an ubiquitin ligase and a deubiquitinating enzyme, and establish a role for USP7 in human neurodevelopmental disease. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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36. Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
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Assimes, Themistocles L., Hólm, Hilma, Kathiresan, Sekar, Reilly, Muredach P., Thorleifsson, Gudmar, Voight, Benjamin F., Erdmann, Jeanette, Willenborg, Christina, Vaidya, Dhananjay, Xie, Changchun, Patterson, Chris C., Morgan, Thomas M., Burnett, Mary Susan, Li, Mingyao, Hlatky, Mark A., Knowles, Joshua W., Thompson, John R., Absher, Devin, Iribarren, Carlos, and Go, Alan
- Subjects
- *
CORONARY disease , *GENETIC polymorphisms , *KINESIN , *MYOCARDIAL infarction , *REGRESSION analysis , *CASE-control method , *CONFIDENCE intervals , *GENETIC carriers , *GENETICS - Abstract
Objectives: We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background: Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods: The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results: A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions: The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. [Copyright &y& Elsevier]
- Published
- 2010
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37. Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.
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Ngcungcu T, Oti M, Sitek JC, Haukanes BI, Linghu B, Bruccoleri R, Stokowy T, Oakeley EJ, Yang F, Zhu J, Sultan M, Schalkwijk J, van Vlijmen-Willems IMJJ, von der Lippe C, Brunner HG, Ersland KM, Grayson W, Buechmann-Moller S, Sundnes O, Nirmala N, Morgan TM, van Bokhoven H, Steen VM, Hull PR, Szustakowski J, Staedtler F, Zhou H, Fiskerstrand T, and Ramsay M
- Subjects
- Case-Control Studies, Cathepsin B genetics, Chromosome Mapping, Chromosomes, Human, Pair 8 genetics, DNA Copy Number Variations, DNA Glycosylases genetics, DNA Glycosylases metabolism, DNA-(Apurinic or Apyrimidinic Site) Lyase genetics, DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism, Epidermis metabolism, Epigenomics, Erythema epidemiology, Female, Genetic Markers, Humans, Keratinocytes metabolism, Keratosis epidemiology, MCF-7 Cells, Male, Norway epidemiology, Pedigree, Skin Diseases, Genetic epidemiology, South Africa epidemiology, Cathepsin B metabolism, Enhancer Elements, Genetic, Erythema genetics, Gene Duplication, Gene Expression Regulation, Keratosis genetics, Skin Diseases, Genetic genetics
- Abstract
Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
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- 2017
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38. Renal teratogens.
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Morgan TM, Jones DP, and Cooper WO
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- Adolescent, Female, Humans, Infant, Newborn, Kidney embryology, Pregnancy, Fetus drug effects, Kidney drug effects, Kidney Diseases congenital, Prenatal Exposure Delayed Effects, Teratogens
- Abstract
In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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39. TM4SF20 ancestral deletion and susceptibility to a pediatric disorder of early language delay and cerebral white matter hyperintensities.
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Wiszniewski W, Hunter JV, Hanchard NA, Willer JR, Shaw C, Tian Q, Illner A, Wang X, Cheung SW, Patel A, Campbell IM, Gelowani V, Hixson P, Ester AR, Azamian MS, Potocki L, Zapata G, Hernandez PP, Ramocki MB, Santos-Cortez RL, Wang G, York MK, Justice MJ, Chu ZD, Bader PI, Omo-Griffith L, Madduri NS, Scharer G, Crawford HP, Yanatatsaneejit P, Eifert A, Kerr J, Bacino CA, Franklin AI, Goin-Kochel RP, Simpson G, Immken L, Haque ME, Stosic M, Williams MD, Morgan TM, Pruthi S, Omary R, Boyadjiev SA, Win KK, Thida A, Hurles M, Hibberd ML, Khor CC, Van Vinh Chau N, Gallagher TE, Mutirangura A, Stankiewicz P, Beaudet AL, Maletic-Savatic M, Rosenfeld JA, Shaffer LG, Davis EE, Belmont JW, Dunstan S, Simmons CP, Bonnen PE, Leal SM, Katsanis N, Lupski JR, and Lalani SR
- Subjects
- Age of Onset, Aging, Premature complications, Aging, Premature ethnology, Aging, Premature pathology, Asian People, Brain metabolism, Brain pathology, Child, Child, Preschool, Chromosomes, Human, Pair 2, Exons, Female, Humans, Language Development Disorders complications, Language Development Disorders ethnology, Language Development Disorders pathology, Leukoencephalopathies complications, Leukoencephalopathies ethnology, Leukoencephalopathies pathology, Magnetic Resonance Imaging, Male, Molecular Sequence Data, Pedigree, Sequence Analysis, DNA, Aging, Premature genetics, Base Sequence, Genetic Predisposition to Disease, Language Development Disorders genetics, Leukoencephalopathies genetics, Sequence Deletion, Tetraspanins genetics
- Abstract
White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showed that the resultant net loss of an exon introduces a premature stop codon, which, in turn, leads to the generation of a stable protein that fails to target to the plasma membrane and accumulates in the cytoplasm. Finally, we report this deletion to be enriched in individuals of Vietnamese Kinh descent, with an allele frequency of about 1%, embedded in an ancestral haplotype. Our data point to a constellation of early language delay and WMH phenotypes, driven by a likely toxic mechanism of TM4SF20 truncation, and highlight the importance of understanding and managing population-specific low-frequency pathogenic alleles., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
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- 2013
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40. Genetic risk score does not correlate with body mass index of Latina women in a clinical trial.
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Coenen KR, Karp SM, Gesell SB, Dietrich MS, Morgan TM, and Barkin SL
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- Adiposity genetics, Adult, Body Composition genetics, Female, Genetic Loci genetics, Genetic Variation, Humans, Middle Aged, Obesity genetics, Residence Characteristics, Risk Factors, White People genetics, Young Adult, Body Mass Index, Genetic Predisposition to Disease, Hispanic or Latino genetics, Randomized Controlled Trials as Topic
- Abstract
Obesity disproportionately affects Latina women. Common genetic variants are convincingly associated with body mass index (BMI) and may be used to create genetic risk scores (GRS) for obesity that could define genetically influenced forms of obesity and alter response to clinical trial interventions. The objective of this study was (1) to identify the frequency and effect size of common obesity genetic variants in Latina women; (2) to determine the clinical utility of a GRS for obesity with Latina women participating in a community-based clinical trial. DNA from 85 Latina women was genotyped for eight genetic variants previously associated with BMI in Caucasians, but not yet assessed in Latina populations. The main outcome measure was the correlation of GRS (sum of eight risk alleles) with BMI, waist circumference, and percent body fat. A majority (83%) of participants had a BMI ≥25. Frequency of loci near FTO, MC4R, and GNPDA2 were lower in Latinas than Caucasians. Association of each locus with BMI was lower in Latinas compared to Caucasians with no significant correlations with BMI. We conclude that an eight locus GRS has no clinical utility for explaining obesity or predicting response to intervention in Latina women participating in a clinical trial., (© 2011 Wiley Periodicals, Inc.)
- Published
- 2011
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41. Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.
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Morgan TM, House JA, Cresci S, Jones P, Allayee H, Hazen SL, Patel Y, Patel RS, Eapen DJ, Waddy SP, Quyyumi AA, Kleber ME, März W, Winkelmann BR, Boehm BO, Krumholz HM, and Spertus JA
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- Acute Coronary Syndrome mortality, Aged, Aged, 80 and over, Aminohydrolases genetics, Cohort Studies, Female, Formate-Tetrahydrofolate Ligase genetics, Genotype, Humans, Kaplan-Meier Estimate, Male, Methylenetetrahydrofolate Dehydrogenase (NADP) genetics, Middle Aged, Multienzyme Complexes genetics, Myocardial Infarction genetics, Myocardial Infarction mortality, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors, White People genetics, Acute Coronary Syndrome genetics, Genetic Variation, Genome-Wide Association Study statistics & numerical data
- Abstract
Background: Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated., Methods: We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients., Results: After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086)., Conclusions: We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.
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- 2011
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42. Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype.
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McGregor TL, Gurnett CA, Dobbs MB, Wise CA, Morcuende JA, Morgan TM, Menon R, and Muglia LJ
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- Adolescent, Amino Acid Oxidoreductases genetics, Case-Control Studies, Cohort Studies, Copper metabolism, Genetic Association Studies, Genotype, Humans, Logistic Models, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Protein-Lysine 6-Oxidase genetics, Scoliosis genetics
- Abstract
Background: Although adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. Work in model organisms, including zebrafish, chickens, and mice, has implicated the lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis., Methods: This was a case-control genetic association study. A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were tested for association with adolescent idiopathic scoliosis by logistic regression with a two degree of freedom genotypic model and gender as a covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an independent replication cohort of 400 cases and 506 controls., Results: No evidence for significant association was found between coding or tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic scoliosis., Conclusions: Despite suggestive evidence in model organisms, common variants and known coding SNPs in the five human lysyl oxidase genes do not confer increased genotypic risk for adolescent idiopathic scoliosis. The above methodology does not address rare variants or individually private mutations in these genes, and future research may focus on this area.
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- 2011
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43. Vaccines are not associated with metabolic events in children with urea cycle disorders.
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Morgan TM, Schlegel C, Edwards KM, Welch-Burke T, Zhu Y, Sparks R, and Summar M
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- Age Distribution, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Hyperammonemia chemically induced, Immunization Schedule, Incidence, Infant, Male, Reference Values, Retrospective Studies, Risk Assessment, Sex Distribution, Urea Cycle Disorders, Inborn diagnosis, Vaccination adverse effects, Vaccines adverse effects, Communicable Disease Control, Hyperammonemia epidemiology, Urea Cycle Disorders, Inborn immunology, Vaccination methods, Vaccines administration & dosage
- Abstract
Background: Despite the success of childhood immunizations in prevention of infectious diseases, questions remain about the safety of vaccines in medically fragile children with inborn errors of metabolism such as urea cycle disorders (UCDs). Patients with UCDs are subject to hyperammonemic episodes (HAEs) after infection, fever, or other stressors., Objective: We sought to assess the risk of HAEs that required urgent care or hospitalization after routine vaccinations in pediatric patients with underlying UCDs., Methods: This was a retrospective investigation of vaccine safety in children with UCDs within the longitudinal Rare Diseases Clinical Research Consortium for UCD. Postvaccination exposure periods were defined as 7 or 21 days after any immunization. The association of vaccines and HAEs was modeled by using conditional Poisson regression, adjusting for age, and using a self-controlled case series method including all patients with ≥1 HAE and with any vaccine exposure., Results: The study enrolled 169 children younger than 18 years. Of these children, 74 had records of at least 1 HAE and at least 1 vaccination. With adjustment for age, there was no increase in relative incidence of HAEs in either the 7-day (1.31 [95% confidence interval (CI): 0.80-2.13]) or 21-day (1.05 [95% CI: 0.74-1.47]) exposure period after vaccination compared with HAEs outside of the vaccination periods. No vaccine type was associated with significantly more HAEs., Conclusions: We found no statistically significant association between childhood immunizations and HAEs in children with UCDs. The results support the safety of immunization in this medically vulnerable population.
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- 2011
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44. National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving Health: August 24-26, 2009.
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Berg AO, Baird MA, Botkin JR, Driscoll DA, Fishman PA, Guarino PD, Hiatt RA, Jarvik GP, Millon-Underwood S, Morgan TM, Mulvihill JJ, Pollin TI, Schimmel SR, Stefanek ME, Vollmer WM, and Williams JK
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- Evidence-Based Medicine, Genome, Human, Humans, Risk Assessment, Family Health, Genetic Predisposition to Disease, Medical History Taking, Primary Health Care
- Published
- 2009
45. Acute effects of nicotine on serum glucose insulin growth hormone and cortisol in healthy smokers.
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Morgan TM, Crawford L, Stoller A, Toth D, Yeo KT, and Baron JA
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- Administration, Cutaneous, Adolescent, Adult, Cross-Over Studies, Double-Blind Method, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Nicotine administration & dosage, Nicotine adverse effects, Smoking Cessation, Blood Glucose metabolism, Human Growth Hormone blood, Hydrocortisone blood, Insulin blood, Nicotine pharmacology, Smoking blood
- Abstract
Cigarette smoking impairs glucose tolerance and alters serum levels of hormones involved in glucose metabolism, but the role of nicotine in such hormonal alterations is not well understood. In order to isolate the effects of transdermal nicotine on serum glucose, insulin, growth hormone, and cortisol in smokers, we conducted a randomized double-blind placebo-controlled cross-over study involving 34 healthy volunteer smokers between 18 and 55 years of age. Administration of a 14-mg transdermal nicotine patch resulted in nonsignificantly lowered fasting quantitative insulin-sensitivity index (P =.11) and a nonsignificant 9.3-mg/dL mean increase in serum glucose levels during a 75-g oral glucose tolerance test (OGTT) at time 60 minutes (P =.12). There were no substantial differences between groups in the areas under the curve (AUCs) for glucose (P =.33) or insulin (P =.79) during the OGTT. Levels of insulin and cortisol also were not significantly altered by nicotine. A secondary finding observed in the overall study group (primarily in females) was that nicotine caused a 29% median decrease in serum growth hormone (P =.02). We conclude that nicotine patches may lead to mild hyperglycemia and lowered insulin sensitivity. Further research is needed to determine the clinical implications of the unexpected finding that nicotine decreased growth hormone levels in female smokers.
- Published
- 2004
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46. The education and medical practice of Dr. James McCune Smith (1813-1865), first black American to hold a medical degree.
- Author
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Morgan TM
- Subjects
- History, 20th Century, Humans, Physicians history, Social Problems history, United States, Black or African American history, Human Rights history
- Abstract
James McCune Smith (1813-1865)--first black American to obtain a medical degree, prominent abolitionist and suffragist, compassionate physician, prolific writer, and public intellectual--has been relatively neglected by historians of medicine. No biography of Smith exists to this day, though he has been the subject of several essays. Born, in his own words, "the son of a self-emancipated bond-woman," and denied admission to colleges in the United States, his native land, Smith earned medical, master's, and baccalaureate degrees at Glasgow University in Scotland. On his return to New York City in 1837, Smith became the first black physician to publish articles in US medical journals. Smith was broadly involved in the anti-slavery and suffrage movements, contributing to and editing abolitionist newspapers and serving as an officer of many organizations for the improvement of social conditions in the black community. In his scientific writings Smith debunked the racial theories in Thomas Jefferson's Notes on the State of Virginia, refuted phrenology and homeopathy, and responded with a forceful statistical critique to the racially biased US Census of 1840. Frederick Douglass, Gerrit Smith, and John Brown personally collaborated with James McCune Smith in the fight for black freedom. As the learned physician-scholar of the abolition movement, Smith was instrumental in making the overthrow of slavery credible and successful.
- Published
- 2003
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