PLoS Articles // Carolina Digital Repository

Works (2111)

61. Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Title Tesim:: Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers
Creator:: Wünsch-Filho, V., Bickeböller, H., Brunnström, H., Aldrich, M.C., Andrew, A.S., Boccia, S., Diergaarde, B., Thomas, S., Cadoni, G., Lesseur, C., Albanes, D., Field, J.K., Lacko, M., Brennan, P., Teare, M.D., Liu, G., Triantafillos, L., Tajara, E.H., Bossé, Y., Clifford, G.M., Ness, A.R., Arnold, S., Le Marchand, L., Kiemeney, L.A., Obeidat, M., Houlston, R.S., McKay, J.D., Amos, C.I., Chen, C., Hung, R.J., Grankvist, K., Caporaso, N.C., Gaborieau, V., Lam, S., Ferreiro-Iglesias, A., Lazarus, P., Olshan, A.F., Bojesen, S.E., Risch, A., Schabath, M.B., Xiao, X., Johansson, M., Rennert, G., Zienolddiny, S., Melander, O., Christiani, D.C., Shete, S., Tardon, A., Ferris, R.L., Weissler, M.C., Timens, W., and Landi, M.T.
Date of publication:: 2021
Abstract Tesim:: Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology and Department of Otolaryngology/Head and Neck Surgery
DOI:: https://doi.org/10.17615/jprp-xr21
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgen.1009254
ISSN:: 1553-7390
Journal Issue:: 3
Journal Title:: PLoS Genetics
Journal Volume:: 17
Keyword:: gene linkage disequilibrium, odds ratio, Genome-Wide Association Study, cancer susceptibility, ABHD8 gene, genotype, TMEM173 gene, larynx squamous cell carcinoma, gene expression, controlled study, TMEM237 gene, STK19 gene, Biomarkers, Tumor, allele, cyclin dependent kinase inhibitor 2B, expression quantitative trait locus, HLA DQA1 gene, gene, tumor marker, CDKN2B AS1 gene, Humans, DNA damage, Genotype, Genetic Predisposition to Disease, protein MDMX, major clinical study, squamous cell lung carcinoma, pathology, genome-wide association study, MDM4 gene, metabolism, signal transduction, genetic risk, pleiotropy, epigenetics, HLA DQA1 antigen, elongation factor 2 kinase, human tissue, squamous cell carcinoma, Carcinoma, Squamous Cell, single nucleotide polymorphism, digestive system tumor, Odds Ratio, genetic variability, Genetic Loci, European, gene locus, tumor suppressor gene, genetic association, meta analysis, BRCA2 protein, Digestive System Neoplasms, oropharynx squamous cell carcinoma, Alleles, human, esophageal squamous cell carcinoma, Article, genetics, Signal Transduction, and genetic predisposition
Language Label:: English
License Label:: CC0 1.0 Universal
Other Affiliation:: Universidade de São Paulo, Georg-August-University Göttingen, Lund University, Vanderbilt University, Dartmouth College, Università Cattolica del Sacro Cuore, University of Pittsburgh, University of Bristol, World Health Organization, National Institutes of Health, University of Liverpool, Maastricht University Medical Center, University Of Sheffield, University of Toronto, School of Medicine of São José do Rio Preto, Laval University, University of Kentucky, University of Hawaii, Radboud University Medical Center, University of British Columbia, The Institute of Cancer Research, London, Baylor college of Medicine, University of Washington, Sinai Health System, Umeå University, British Columbia Cancer Agency, Washington State University, , Herlev and Gentofte Hospital, University of Salzburg, H. Lee Moffitt Cancer Center and Research Institute, Carmel Medical Center, National Institute of Occupational Health, Massachusetts General Hospital, The University of Texas M.D. Anderson Cancer Center, University of Oviedo, and University of Groningen
Person:: Wünsch-Filho, V., Bickeböller, H., Brunnström, H., Aldrich, M.C., Andrew, A.S., Boccia, S., Diergaarde, B., Thomas, S., Cadoni, G., Lesseur, C., Albanes, D., Field, J.K., Lacko, M., Brennan, P., Teare, M.D., Liu, G., Triantafillos, L., Tajara, E.H., Bossé, Y., Clifford, G.M., Ness, A.R., Arnold, S., Le Marchand, L., Kiemeney, L.A., Obeidat, M., Houlston, R.S., McKay, J.D., Amos, C.I., Chen, C., Hung, R.J., Grankvist, K., Caporaso, N.C., Gaborieau, V., Lam, S., Ferreiro-Iglesias, A., Lazarus, P., Olshan, A.F., Bojesen, S.E., Risch, A., Schabath, M.B., Xiao, X., Johansson, M., Rennert, G., Zienolddiny, S., Melander, O., Christiani, D.C., Shete, S., Tardon, A., Ferris, R.L., Weissler, M.C., Timens, W., and Landi, M.T.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: 02519e26-5ee9-494f-b494-f24c314e3d5e

62. Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach

Title Tesim:: Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach
Creator:: the National Birth Defects Prevention Study, Li, J., Romitti, P.A., Nembhard, W.N., Olshan, A., Browne, M.L., Shaw, G.M., Orloff, M., Jenkins, M.M., Patel, J., Tang, X., Hobbs, C.A., Werler, M.M., Finnell, R.H., Bircan, E., and Botto, L.D.
Date of publication:: 2021
Abstract Tesim:: Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/4h14-yj71
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgen.1009413
ISSN:: 1553-7390
Journal Issue:: 3
Journal Title:: PLoS Genetics
Journal Volume:: 17
Keyword:: progeny, DNA, MGMT gene, linear system, inheritance, heart disease, Male, father, live birth, genetics, risk assessment, mother, Young Adult, genetic variation, chromosomal mapping, risk factor, Article, Female, Alleles, genetic variability, male, pathogenesis, infant, Genetic Predisposition to Disease, gene, odds ratio, Genetic Variation, Phenotype, Adult, sulfation, female, adenine, human, phenotype, genetic predisposition, adult, Cardiomyopathy, Hypertrophic, Familial, Middle Aged, GSTA3 gene, Chromosome Mapping, familial hypertrophic cardiomyopathy, Odds Ratio, Polymorphism, Single Nucleotide, transsulfuration, guanine, Humans, major clinical study, genotype, Inheritance Patterns, Risk Assessment, metabolism, congenital heart malformation, confidence interval, Heart Defects, Congenital, folic acid, family, obstructive heart defect, middle aged, RFC1 gene, homocysteine, Genotype, controlled study, allele, young adult, and single nucleotide polymorphism
Language Label:: English
License Label:: CC0 1.0 Universal
Other Affiliation:: , University of Arkansas for Medical Sciences, University of Iowa, University at Albany, Stanford University, Centers for Disease Control and Prevention, Rady Children’s Institute for Genomic Medicine, Boston University, Baylor College of Medicine, and University of Utah
Person:: the National Birth Defects Prevention Study, Li, J., Romitti, P.A., Nembhard, W.N., Olshan, A., Browne, M.L., Shaw, G.M., Orloff, M., Jenkins, M.M., Patel, J., Tang, X., Hobbs, C.A., Werler, M.M., Finnell, R.H., Bircan, E., and Botto, L.D.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: b03269df-9693-4de9-a9c2-cf2384bdab0b

63. A high throughput, functional screen of human Body Mass Index GWAS loci using tissue-specific RNAi Drosophila melanogaster crosses

Title Tesim:: A high throughput, functional screen of human Body Mass Index GWAS loci using tissue-specific RNAi Drosophila melanogaster crosses
Creator:: North, K.E., Fink, J.L., Cupples, L.A., Liu, C.-T., Kraja, A.T., Borecki, I.B., Baranski, T.J., Lenzini, P.A., Province, M.A., and Feitosa, M.
Date of publication:: 2018
Abstract Tesim:: Human GWAS of obesity have been successful in identifying loci associated with adiposity, but for the most part, these are non-coding SNPs whose function, or even whose gene of action, is unknown. To help identify the genes on which these human BMI loci may be operating, we conducted a high throughput screen in Drosophila melanogaster. Starting with 78 BMI loci from two recently published GWAS meta-analyses, we identified fly orthologs of all nearby genes (± 250KB). We crossed RNAi knockdown lines of each gene with flies containing tissue-specific drivers to knock down (KD) the expression of the genes only in the brain and the fat body. We then raised the flies on a control diet and compared the amount of fat/triglyceride in the tissue-specific KD group compared to the driver-only control flies. 16 of the 78 BMI GWAS loci could not be screened with this approach, as no gene in the 500-kb region had a fly ortholog. Of the remaining 62 GWAS loci testable in the fly, we found a significant fat phenotype in the KD flies for at least one gene for 26 loci (42%) even after correcting for multiple comparisons. By contrast, the rate of significant fat phenotypes in RNAi KD found in a recent genome-wide Drosophila screen (Pospisilik et al. (2010) is ~5%. More interestingly, for 10 of the 26 positive regions, we found that the nearest gene was not the one that showed a significant phenotype in the fly. Specifically, our screen suggests that for the 10 human BMI SNPs rs11057405, rs205262, rs9925964, rs9914578, rs2287019, rs11688816, rs13107325, rs7164727, rs17724992, and rs299412, the functional genes may NOT be the nearest ones (CLIP1, C6orf106, KAT8, SMG6, QPCTL, EHBP1, SLC39A8, ADPGK /ADPGK-AS1, PGPEP1, KCTD15, respectively), but instead, the specific nearby cis genes are the functional target (namely: ZCCHC8, VPS33A, RSRC2; SPDEF, NUDT3; PAGR1; SETD1, VKORC1; SGSM2, SRR; VASP, SIX5; OTX1; BANK1; ARIH1; ELL; CHST8, respectively). The study also suggests further functional experiments to elucidate mechanism of action for genes evolutionarily conserved for fat storage.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/w9v0-ch68
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgen.1007222
Journal Issue:: 4
Journal Title:: PLoS Genetics
Journal Volume:: 14
Keyword:: EHBP1 gene, Polymorphism, Single Nucleotide, SGSM2 gene, Adipose Tissue, SRR gene, KAT8 gene, C6orf106 gene, quantitative trait locus, animal, mouse, gene locus, Animals, cross breeding, body mass, Article, ADPGK gene, adipose tissue, SETD1 gene, ADPGK AS1 gene, gene, OTX1 gene, ARIH1 gene, SLC39A8 gene, PAGR1 gene, controlled study, single nucleotide polymorphism, Drosophila melanogaster, obesity, genetics, genome-wide association study, CHST8 gene, RSRC2 gene, female, adult, male, RNA Interference, Mice, QPCTL gene, nonhuman, ZCCHC8 gene, phenotype, intron, Humans, Obesity, gene knockdown, VKORC1 gene, PGPEP1 gene, VPS33A gene, RNA interference, Genome-Wide Association Study, Body Mass Index, SPDEF gene, human tissue, KCTD15 gene, human, SIX5 gene, VASP gene, Crosses, Genetic, CLIP1 gene, SMG6 gene, NUDT3 gene, ELL gene, Quantitative Trait Loci, BANK1 gene, and genetic conservation
Language Label:: English
License Label:: Attribution 4.0 International
Other Affiliation:: , Washington University, Boston University School of Public Health, Washington University School of Medicine, and University of Washington
Person:: North, K.E., Fink, J.L., Cupples, L.A., Liu, C.-T., Kraja, A.T., Borecki, I.B., Baranski, T.J., Lenzini, P.A., Province, M.A., and Feitosa, M.
Rights Statement Label:: In Copyright
Source:: d0158ab9-cfe6-4125-9af3-7dacf2cf8933

64. A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program

Title Tesim:: A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program
Creator:: Pyarajan, S., Ho, Y.-L.A., Zhao, H., Marouli, E., Raghavan, S., Hunter-Zinck, H., Huffman, J.E., Wilson, P.W.F., Tsao, P.S., O'Donnell, C.J., Gaziano, J.M., Assimes, T.L., Lange, L.A., Sun, Y.V., Lange, E., Tcheandjieu, C., Cho, K., Liu, C., Huang, J., Voight, B.F., Litkowski, E., North, K.E., Hauser, E.R., and Chang, K.-M.
Date of publication:: 2022
Abstract Tesim:: Background Height has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank. Methods and findings Analyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders. Conclusions We conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/gaa4-wv47
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgen.1010193
ISSN:: 1553-7390
Journal Issue:: 6
Journal Title:: PLoS Genetics
Journal Volume:: 18
Keyword:: adult, veterans health service, middle aged, Veterans, hyperlipidemia, single nucleotide polymorphism, female, controlled study, Humans, biobank, Atrial Fibrillation, ischemic heart disease, genetic predisposition, electronic health record, meta analysis, Hypertension, peripheral neuropathy, Adult, hypertension, cardiovascular disease, genetic risk, male, diabetes mellitus, atrial fibrillation, genetics, Polymorphism, Single Nucleotide, body mass, veteran, genetic association, genetic association study, human, Black person, Genome-Wide Association Study, genome-wide association study, body height, Genetic Predisposition to Disease, health care system, risk factor, Caucasian, ischemia, Article, pleiotropy, phenome wide association study, and Mendelian randomization analysis
Language Label:: English
License Label:: CC0 1.0 Universal
Other Affiliation:: Brigham and Women’s Hospital, Veterans Affairs Boston Healthcare System, Veterans Affairs Connecticut Healthcare System, Queen Mary University of London, University of Colorado Anschutz Medical Campus, Emory University, Duke University Medical Center, Harvard Medical School, Stanford University, Brigham and Women's Hospital, Southern University of Science and Technology, University of Pennsylvania, Veterans Affairs Eastern Colorado Health Care System, and
Person:: Pyarajan, S., Ho, Y.-L.A., Zhao, H., Marouli, E., Raghavan, S., Hunter-Zinck, H., Huffman, J.E., Wilson, P.W.F., Tsao, P.S., O'Donnell, C.J., Gaziano, J.M., Assimes, T.L., Lange, L.A., Sun, Y.V., Lange, E., Tcheandjieu, C., Cho, K., Liu, C., Huang, J., Voight, B.F., Litkowski, E., North, K.E., Hauser, E.R., and Chang, K.-M.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: 09bd3d0a-355a-4af1-87d3-0ab083173a87

65. Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells

Title Tesim:: Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells
Creator:: Sarabipour S., Bautch V.L., Quigley K.M., Kinghorn K., Kovacs-Kasa A., Gabhann F.M., and Annex B.H.
Date of publication:: 2024
Abstract Tesim:: The vascular endothelial growth factor (VEGF) family of cytokines are key drivers of blood vessel growth and remodeling. These ligands act via multiple VEGF receptors (VEGFR) and co-receptors such as Neuropilin (NRP) expressed on endothelial cells. These membrane- associated receptors are not solely expressed on the cell surface, they move between the surface and intracellular locations, where they can function differently. The location of the receptor alters its ability to 'see' (access and bind to) its ligands, which regulates receptor activation; location also alters receptor exposure to subcellularly localized phosphatases, which regulates its deactivation. Thus, receptors in different subcellular locations initiate different signaling, both in terms of quantity and quality. Similarly, the local levels of co-expression of other receptors alters competition for ligands. Subcellular localization is controlled by intracellular trafficking processes, which thus control VEGFR activity; therefore, to understand VEGFR activity, we must understand receptor trafficking. Here, for the first time, we simultaneously quantify the trafficking of VEGFR1, VEGFR2, and NRP1 on the same cells-specifically human umbilical vein endothelial cells (HUVECs). We build a computational model describing the expression, interaction, and trafficking of these receptors, and use it to simulate cell culture experiments. We use new quantitative experimental data to parameterize the model, which then provides mechanistic insight into the trafficking and localization of this receptor network. We show that VEGFR2 and NRP1 trafficking is not the same on HUVECs as on non-human ECs; and we show that VEGFR1 trafficking is not the same as VEGFR2 trafficking, but rather is faster in both internalization and recycling. As a consequence, the VEGF receptors are not evenly distributed between the cell surface and intracellular locations, with a very low percentage of VEGFR1 being on the cell surface, and high levels of NRP1 on the cell surface. Our findings have implications both for the sensing of extracellular ligands and for the composition of signaling complexes at the cell surface versus inside the cell.
Resource type:: Article
Affiliation Label Tesim:: Department of Biology
DOI:: https://doi.org/10.17615/tx4v-b241
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pcbi.1011798
ISSN:: 1553-734X
Journal Issue:: 2-Feb
Journal Title:: PLoS Computational Biology
Journal Volume:: 20
Keyword:: Receptor activity, simulation, Receptors, Vascular Endothelial Growth Factor, neuropilin 1, Phosphorylation, whole cell, Blood vessel growth, Blood vessels, endothelium cell, Blood vessel remodeling, Cell engineering, Cell signaling, protein phosphorylation, Human endothelial cells, polyacrylamide gel electrophoresis, cycloheximide, Neuropilin-1, Cell surfaces, sensitivity analysis, vasculotropin receptor 2, Signal Transduction, Cytokines, Humans, mathematical model, endocytosis, biochemical analysis, metabolism, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A, phosphorylation, Western blotting, signal transduction, immunoblotting, Growth and remodeling, HUVEC cell line, Ligands, Vascular Endothelial Growth Factor Receptor-2, chloroquine, protein aggregation, Cell culture, Human Umbilical Vein Endothelial Cells, Vascular endothelial growth factor receptor, nonhuman, small interfering RNA, Cell membranes, gene knockdown, controlled study, Article, Endothelial cells, Vascular endothelial growth factor, dynamics, Location, umbilical vein endothelial cell, human cell, vasculotropin A, Human umbilical vein endothelial cells, human, vasculotropin receptor 1, biotin, and vasculotropin receptor
Language Label:: English
License Label:: Attribution 4.0 International
Other Affiliation:: Johns Hopkins University, , and Augusta University
Person:: Sarabipour S., Bautch V.L., Quigley K.M., Kinghorn K., Kovacs-Kasa A., Gabhann F.M., and Annex B.H.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: c02004eb-45ff-4312-b0ec-6970d183d808

66. The longitudinal association of stressful life events with depression remission among SHARP trial participants with depression and hypertension or diabetes in Malawi

Title Tesim:: The longitudinal association of stressful life events with depression remission among SHARP trial participants with depression and hypertension or diabetes in Malawi
Creator:: Masiye, Jones, Akello, Harriet, Udedi, Michael, Hosseinipour, Mina C., Dussault, Josée M., Zimba, Chifundo C., Pence, Brian W., Gaynes, Bradley N., Malava, Jullita Kenala, and Landrum, Kelsey R.
Date of publication:: 2024
Abstract Tesim:: Depressive disorders are leading contributors to morbidity in low- and middle-income countries and are particularly prevalent among people with non-communicable diseases (NCD). Stressful life events (SLEs) are risk factors for, and can help identify those at risk of, severe depressive illness requiring more aggressive treatment. Yet, research on the impact of SLEs on the trajectory of depressive symptoms among NCD patients indicated for depression treatment is lacking, especially in low resource settings. This study aims to estimate the longitudinal association of SLEs at baseline with depression remission achievement at three, six, and 12 months among adults with either hypertension or diabetes and comorbid depression identified as being eligible for depression treatment. Participants were recruited from 10 NCD clinics in Malawi from May 2019-December 2021. SLEs were measured by the Life Events Survey and depression remission was defined as achieving a Patient Health Questionaire-9 (PHQ-9) score <5 at follow-up. The study population (n = 737) consisted predominately of females aged 50 or higher with primary education and current employment. At baseline, participants reported a mean of 3.5 SLEs in the prior three months with 90% reporting ≥1 SLE. After adjustment, each additional SLE was associated with a lower probability of achieving depression remission at three months (cumulative incidence ratio (CIR) 0.94; 95% confidence interval: 0.90, 0.98, p = 0.002), six months (0.95; 0.92, 0.98, p = 0.002) and 12 months (0.96; 0.94, 0.99, p = 0.011). Re-expressed per 3-unit change, the probability of achieving depression remission at three, six, and 12 months was 0.82, 0.86, and 0.89 times lower per 3 SLEs (the median number of SLEs). Among NCD patients identified as eligible for depression treatment, recent SLEs at baseline were associated with lower probability of achieving depression remission at three, six, and 12 months. Findings suggest that interventions addressing SLEs during integrated NCD and depression care interventions (e.g., teaching and practicing SLE coping strategies) may improve success of depression treatment among adult patient populations in low-resource settings and may help identify those at risk of severe and treatment resistant depression.
Resource type:: Article
Affiliation Label Tesim:: UNC Project-Malawi, Department of Medicine, and Department of Epidemiology
DOI:: https://doi.org/10.17615/5sbx-p543
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pone.0298546
ISSN:: 1932-6203
Journal Issue:: 2
Journal Title:: PLOS ONE
Journal Volume:: 19
Keyword:: Noncommunicable diseases, Alcohols, SARS CoV 2, Mental health and psychiatry, Depression, Malawi, Pandemics, and Medical risk factors
Language Label:: English
License Label:: Attribution 4.0 International
Other Affiliation:: Malawi Ministry of Health and
Page Start:: e0298546
Person:: Masiye, Jones, Akello, Harriet, Udedi, Michael, Hosseinipour, Mina C., Dussault, Josée M., Zimba, Chifundo C., Pence, Brian W., Gaynes, Bradley N., Malava, Jullita Kenala, and Landrum, Kelsey R.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: d5ce429c-a313-46ff-bd0e-2bc4346c709d

67. Simultaneous detection and quantification of multiple pathogen targets in wastewater

Title Tesim:: Simultaneous detection and quantification of multiple pathogen targets in wastewater
Creator:: Rao, Gouthami, Lai, Amanda, Huang, Ching-Hua, Capone, Drew, Zhu, Kevin, Linden, Yarrow, Knoble, Abigail, Kim, Juhee, Brown, Joe, Bivins, Aaron, and Clark, Ryan
Date of publication:: 2024
Abstract Tesim:: Wastewater-based epidemiology has emerged as a critical tool for public health surveillance, building on decades of environmental surveillance work for pathogens such as poliovirus. Work to date has been limited to monitoring a single pathogen or small numbers of pathogens in targeted studies; however, few studies consider simultaneous quantitative analysis of a wide variety of pathogens, which could greatly increase the utility of wastewater surveillance. We developed a novel quantitative multi-pathogen surveillance approach (35 pathogen targets including bacteria, viruses, protozoa, and helminths) using TaqMan Array Cards (TAC) and applied the method on concentrated wastewater samples collected at four wastewater treatment plants in Atlanta, GA from February to October of 2020. From sewersheds serving approximately 2 million people, we detected a wide range of targets including many we expected to find in wastewater (e.g., enterotoxigenic E. coli and Giardia in 97% of 29 samples at stable concentrations) as well as unexpected targets including Strongyloides stercoralis (a human threadworm rarely observed in the USA). Other notable detections included SARS-CoV-2, but also several pathogen targets that are not commonly included in wastewater surveillance like Acanthamoeba spp., Balantidium coli, Entamoeba histolytica, astrovirus, norovirus, and sapovirus. Our data suggest broad utility in expanding the scope of enteric pathogen surveillance in wastewaters, with potential for application in a variety of settings where pathogen quantification in fecal waste streams can inform public health surveillance and selection of control measures to limit infections.
Resource type:: Article
Affiliation Label Tesim:: Department of Environmental Sciences and Engineering
DOI:: https://doi.org/10.17615/xvgy-dm11
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pwat.0000224
ISSN:: 2767-3219
Journal Issue:: 2
Journal Title:: PLOS Water
Journal Volume:: 3
Keyword:: Pathogens, SARS CoV 2, Mitochondrial DNA, Public and occupational health, Bacterial pathogens, Infectious disease surveillance, Escherichia coli, and Milk
Language Label:: English
License Label:: Attribution 4.0 International
Other Affiliation:: , Georgia Institute of Technology, Indiana University, Bloomington, and Louisiana State University
Page Start:: e0000224
Person:: Rao, Gouthami, Lai, Amanda, Huang, Ching-Hua, Capone, Drew, Zhu, Kevin, Linden, Yarrow, Knoble, Abigail, Kim, Juhee, Brown, Joe, Bivins, Aaron, and Clark, Ryan
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: 5029c882-77d2-49be-8952-669b6ccf007f

68. IntroUNET: Identifying introgressed alleles via semantic segmentation

Title Tesim:: IntroUNET: Identifying introgressed alleles via semantic segmentation
Creator:: Flagel, Lex, Ray, Dylan D., and Schrider, Daniel R.
Date of publication:: 2024
Abstract Tesim:: A growing body of evidence suggests that gene flow between closely related species is a widespread phenomenon. Alleles that introgress from one species into a close relative are typically neutral or deleterious, but sometimes confer a significant fitness advantage. Given the potential relevance to speciation and adaptation, numerous methods have therefore been devised to identify regions of the genome that have experienced introgression. Recently, supervised machine learning approaches have been shown to be highly effective for detecting introgression. One especially promising approach is to treat population genetic inference as an image classification problem, and feed an image representation of a population genetic alignment as input to a deep neural network that distinguishes among evolutionary models (i.e. introgression or no introgression). However, if we wish to investigate the full extent and fitness effects of introgression, merely identifying genomic regions in a population genetic alignment that harbor introgressed loci is insufficient—ideally we would be able to infer precisely which individuals have introgressed material and at which positions in the genome. Here we adapt a deep learning algorithm for semantic segmentation, the task of correctly identifying the type of object to which each individual pixel in an image belongs, to the task of identifying introgressed alleles. Our trained neural network is thus able to infer, for each individual in a two-population alignment, which of those individual’s alleles were introgressed from the other population. We use simulated data to show that this approach is highly accurate, and that it can be readily extended to identify alleles that are introgressed from an unsampled “ghost” population, performing comparably to a supervised learning method tailored specifically to that task. Finally, we apply this method to data from Drosophila, showing that it is able to accurately recover introgressed haplotypes from real data. This analysis reveals that introgressed alleles are typically confined to lower frequencies within genic regions, suggestive of purifying selection, but are found at much higher frequencies in a region previously shown to be affected by adaptive introgression. Our method’s success in recovering introgressed haplotypes in challenging real-world scenarios underscores the utility of deep learning approaches for making richer evolutionary inferences from genomic data.
Resource type:: Article
Affiliation Label Tesim:: Department of Genetics
DOI:: https://doi.org/10.17615/ytdn-mt59
Edition:: Postprint
Identifier:: https://doi.org/10.1371/journal.pgen.1010657
ISSN:: 1553-7404
Journal Issue:: 2
Journal Title:: PLOS Genetics
Journal Volume:: 20
Keyword:: Simulation and modeling, Population genetics, Neural networks, Drosophila melanogaster, Haplotypes, Drosophila, Introgression, and Invertebrate genomics
Language Label:: English
License Label:: Attribution 4.0 International
Other Affiliation:: University of Minnesota and
Page Start:: e1010657
Person:: Flagel, Lex, Ray, Dylan D., and Schrider, Daniel R.
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: 3156db08-9d25-4997-9e37-beaf7c9e2882

69. HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999–2016

Title Tesim:: HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999–2016
Creator:: Reynolds, Steven J., Chang, Larry W., Lessler, Justin, Alamo, Stella, Kagaayi, Joseph, Popoola, Victor O., Wawer, Maria J., Kabatesi, Donna, Lutalo, Tom, Tobian, Aaron A. R., Santelli, John, Grabowski, M. Kate, Ssekubugu, Robert, Mills, Lisa A., Gray, Ronald H., Kigozi, Grace, Serwadda, David, Ssekasanvu, Joseph, Ndyanabo, Anthony, Kigozi, Godfrey, and Nalugoda, Fred
Date of publication:: 2024
Abstract Tesim:: Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23–0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18–0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/4000-cs59
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgph.0002891
ISSN:: 2767-3375
Journal Issue:: 2
Journal Title:: PLOS Global Public Health
Journal Volume:: 4
Keyword:: HIV, HIV epidemiology, Agriculture, HIV infections, Medical risk factors, Transportation, HIV prevention, and Uganda
Language Label:: English
License Label:: CC0 1.0 Universal
Other Affiliation:: Johns Hopkins School of Medicine, Rakai Health Sciences Program, , Centers for Disease Control and Prevention Uganda, Johns Hopkins Bloomberg School of Public Health, and Columbia University
Page Start:: e0002891
Person:: Reynolds, Steven J., Chang, Larry W., Lessler, Justin, Alamo, Stella, Kagaayi, Joseph, Popoola, Victor O., Wawer, Maria J., Kabatesi, Donna, Lutalo, Tom, Tobian, Aaron A. R., Santelli, John, Grabowski, M. Kate, Ssekubugu, Robert, Mills, Lisa A., Gray, Ronald H., Kigozi, Grace, Serwadda, David, Ssekasanvu, Joseph, Ndyanabo, Anthony, Kigozi, Godfrey, and Nalugoda, Fred
Publisher:: Public Library of Science
Rights Statement Label:: In Copyright
Source:: fa12876f-fb82-4eaf-b18d-37ad83fb2b85

70. Factors associated with COVID-19 vaccine uptake and hesitancy among healthcare workers in the Democratic Republic of the Congo

Title Tesim:: Factors associated with COVID-19 vaccine uptake and hesitancy among healthcare workers in the Democratic Republic of the Congo
Creator:: Nzaji, Michel K., Sessoms, Dana, Kapit, Anselme Manyong, Fogarty, Alanna S., Meyou, Shanice Fezeu, Stolka, Kristen B., Lungayo, Christophe Luhata, Bene, Aime Cikomola Mwana, Standley, Claire J., de Dieu Kamenga, Jean, and MacDonald, Pia D. M.
Date of publication:: 2024
Abstract Tesim:: Vaccination is a critical intervention to reduce morbidity and mortality and limit strain on health systems caused by COVID-19. The slow pace of COVID-19 vaccination uptake observed in some settings raises concerns about COVID-19 vaccine hesitancy. The Democratic Republic of the Congo experienced logistical challenges and low uptake at the start of vaccine distribution, leading to one of the lowest overall COVID-19 vaccine coverage rates in the world in 2021. This study assessed the magnitude and associated factors of COVID-19 vaccine uptake among healthcare workers (HCWs) in seven provinces in DRC. We implemented a cross-sectional Knowledge, Attitudes, and Practices (KAP) questionnaire targeting HCWs, administered by trained data collectors in Haut-Katanga, Kasaï Orientale, Kinshasa, Kongo Centrale, Lualaba, North Kivu, and South Kivu provinces. Data were summarized and statistical tests were performed to assess factors associated with vaccine uptake. HCWs across the seven provinces completed the questionnaire (N = 5,102), of whom 46.3% had received at least one dose of COVID-19 vaccine. Older age, being married, being a medical doctor, being a rural resident, and having access to or having previously worked in a COVID-19 vaccination site were all strongly associated with vaccination uptake. Vaccinated individuals most frequently cited protection of themselves, their families, and their communities as motivations for being vaccinated, whereas unvaccinated individuals were most concerned about safety, effectiveness, and risk of severe side effects. The findings suggest an opinion divide between vaccine-willing and vaccine-hesitant HCWs. A multidimensional approach may be needed to increase the acceptability of the COVID-19 vaccine for HCWs. Future vaccine campaign messaging could center around the positive impact of vaccination on protecting friends, family, and the community, and also emphasize the safety and very low risk of adverse effects. These types of messages may further be useful when planning future immunization campaigns with new vaccines.
Resource type:: Article
Affiliation Label Tesim:: Department of Epidemiology
DOI:: https://doi.org/10.17615/swqy-r903
Edition:: Publisher
Identifier:: https://doi.org/10.1371/journal.pgph.0002772
ISSN:: 2767-3375
Journal Issue:: 2
Journal Title:: PLOS Global Public Health
Journal Volume:: 4
Keyword:: Vaccines, Viral vaccines, COVID 19, Medical risk factors, Vaccine development, Vaccination and immunization, Questionnaires, and Virus testing
Language Label:: English
License Label:: Attribution 4.0 International
ORCID:
Other Affiliation:: RTI International, Georgetown University, Ministry of Public Health, and
Page Start:: e0002772
Person:: Nzaji, Michel K., Sessoms, Dana, Kapit, Anselme Manyong, Fogarty, Alanna S., Meyou, Shanice Fezeu, Stolka, Kristen B., Lungayo, Christophe Luhata, Bene, Aime Cikomola Mwana, Standley, Claire J., de Dieu Kamenga, Jean, and MacDonald, Pia D. M.
Publisher:: Public Library of Science
Source:: 978bfc31-3bd8-4054-813b-29556ac6abab

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