182 results on '"Campbell, Desmond"'
Search Results
2. A workshop to showcase the diversity of scientists to middle school students
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Marshall, Andrea G., primary, Neikirk, Kit, additional, Stephens, Dominique, additional, Garza-Lopez, Edgar, additional, Vue, Zer, additional, Beasley, Heather K., additional, Doe, Yelena Janumyan, additional, Campbell, Desmond, additional, Fears, Letimicia, additional, Alghanem, Ahmad, additional, Spencer, Elsie C., additional, Scudese, Estevão, additional, Owens, Beverly, additional, Vang, Chia, additional, Morton, Derrick J., additional, Conley, Zachary, additional, and Hinton, Antentor, additional
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- 2024
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3. Effects of increased body mass index on employment status: a Mendelian randomisation study
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Campbell, Desmond D., Green, Michael, Davies, Neil, Demou, Evangelia, Ward, Joey, Howe, Laura D., Harrison, Sean, Johnston, Keira J. A., Strawbridge, Rona J., Popham, Frank, Smith, Daniel J., Munafò, Marcus R., and Katikireddi, Srinivasa Vittal
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- 2021
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4. A workshop on mitochondria for students to improve understanding of science and hypothesis forming
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Marshall, Andrea G., primary, Neikirk, Kit, additional, Stephens, Dominique, additional, Garza-Lopez, Edgar, additional, Vue, Zer, additional, Beasley, Heather K., additional, Janumyan Doe, Yelena, additional, Campbell, Desmond, additional, Fears, Letimicia, additional, Alghanem, Ahmad, additional, Spencer, Elsie C., additional, Scudese, Estevão, additional, Owens, Beverly, additional, Vang, Chia, additional, Morton, Derrick J., additional, Conley, Zachary, additional, and Hinton, Antentor, additional
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- 2023
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- View/download PDF
5. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.
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Yu, Dongmei, Mathews, Carol A, Scharf, Jeremiah M, Neale, Benjamin M, Davis, Lea K, Gamazon, Eric R, Derks, Eske M, Evans, Patrick, Edlund, Christopher K, Crane, Jacquelyn, Fagerness, Jesen A, Osiecki, Lisa, Gallagher, Patience, Gerber, Gloria, Haddad, Stephen, Illmann, Cornelia, McGrath, Lauren M, Mayerfeld, Catherine, Arepalli, Sampath, Barlassina, Cristina, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Berrió, Gabriel Bedoya, Bienvenu, O Joseph, Black, Donald W, Bloch, Michael H, Brentani, Helena, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Campbell, Desmond D, Cappi, Carolina, Silgado, Julio C Cardona, Cavallini, Maria C, Chavira, Denise A, Chouinard, Sylvain, Cook, Edwin H, Cookson, MR, Coric, Vladimir, Cullen, Bernadette, Cusi, Daniele, Delorme, Richard, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald L, Girard, Simon L, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Grünblatt, Edna, Hardy, John, Heiman, Gary A, Hemmings, Sian MJ, Herrera, Luis D, Hezel, Dianne M, Hoekstra, Pieter J, Jankovic, Joseph, Kennedy, James L, King, Robert A, Konkashbaev, Anuar I, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L, Lupoli, Sara, Macciardi, Fabio, Maier, Wolfgang, Manunta, Paolo, Marconi, Maurizio, McCracken, James T, Mesa Restrepo, Sandra C, Moessner, Rainald, Moorjani, Priya, Morgan, Jubel, Muller, Heike, Murphy, Dennis L, Naarden, Allan L, Nurmi, Erika, Ochoa, William Cornejo, Ophoff, Roel A, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, and Pollak, Yehuda
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Humans ,Tourette Syndrome ,Severity of Illness Index ,Obsessive-Compulsive Disorder ,Psychiatric Status Rating Scales ,Comorbidity ,Polymorphism ,Single Nucleotide ,Adult ,Female ,Male ,Genome-Wide Association Study ,Human Genome ,Genetics ,Brain Disorders ,Serious Mental Illness ,Neurodegenerative ,Prevention ,Anxiety Disorders ,Mental Health ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectiveObsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.MethodThe authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.ResultsAlthough no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).ConclusionsPrevious work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
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- 2015
6. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
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Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Konkashbaev, Anuar I, Derks, Eske M, Neale, Benjamin M, Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J, Bloch, Michael H, Blom, Rianne M, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C, Cath, Danielle C, Cavallini, Maria C, Chavira, Denise A, Chouinard, Sylvain, Conti, David V, Cook, Edwin H, Coric, Vladimir, Cullen, Bernadette A, Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K, Egberts, Karin, Falkai, Peter, Fernandez, Thomas V, Gallagher, Patience J, Garrido, Helena, Geller, Daniel, Girard, Simon L, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A, Hemmings, Sian M. J, Hounie, Ana G, Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A, Kennedy, James L, King, Robert A, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L, Macciardi, Fabio, McCracken, James T, McGrath, Lauren M, Mesa Restrepo, Sandra C, Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L, Naarden, Allan L, Ochoa, William Cornejo, Ophoff, Roel A, Osiecki, Lisa, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L, Renner, Tobias J, Reus, Victor I, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Romero, Roxana, Rosàrio, Maria C, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, and Smit, Jan H
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Missing Heritability ,Tic Disorders ,Neuropsychiatric Disorders ,Complex Diseases ,Common Snps ,Gilles ,Family ,Brain ,Expression ,Autism - Published
- 2013
7. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.
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Chouinard, Sylvain, Conti, David, Cook, Edwin, Coric, Vladimir, Cullen, Bernadette, Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Gallagher, Patience, Garrido, Helena, Geller, Daniel, Girard, Simon, Grabe, Hans, Grados, Marco, Greenberg, Benjamin, Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary, Hemmings, Sian, Hounie, Ana, Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael, Kennedy, James, King, Robert, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Davis, Lea, Yu, Dongmei, Keenan, Clare, Gamazon, Eric, Konkashbaev, Anuar, Derks, Eske, Neale, Benjamin, Yang, Jian, Lee, S, Evans, Patrick, Barr, Cathy, Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel, Bienvenu, Oscar, Bloch, Michael, Blom, Rianne, Bruun, Ruth, Budman, Cathy, Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio, Cath, Danielle, Cavallini, Maria, McCracken, James, McGrath, Lauren, Mesa Restrepo, Sandra, Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis, Naarden, Allan, Ochoa, William, Osiecki, Lisa, Pakstis, Andrew, Pato, Michele, Pato, Carlos, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott, Renner, Tobias, Richter, Margaret, Riddle, Mark, Robertson, Mary, Romero, Roxana, Rosàrio, Maria, Rosenberg, David, Rouleau, Guy, Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey, Smit, Jan, Stein, Dan, Strengman, E, Tischfield, Jay, Valencia Duarte, Ana, Vallada, Homero, and Van Nieuwerburgh, Filip
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Gene Frequency ,Genome-Wide Association Study ,Humans ,Obsessive-Compulsive Disorder ,Phenotype ,Polymorphism ,Single Nucleotide ,Quantitative Trait ,Heritable ,Tourette Syndrome - Abstract
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
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- 2013
8. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.
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Nag, Abhishek, Bochukova, Elena, Kremeyer, Barbara, Campbell, Desmond, Muller, Heike, Valencia-Duarte, Ana, Cardona, Julio, Rivas, Isabel, Mesa, Sandra, Cuartas, Mauricio, Garcia, Jharley, Bedoya, Gabriel, Cornejo, William, Herrera, Luis, Romero, Roxana, Fournier, Eduardo, McGrath, Lauren, Yu, Dongmei, Cook, Ed, Wang, Kai, Scharf, Jeremiah, Pauls, David, Plagnol, Vincent, Ruiz-Linares, Andrés, Farooqi, I, Reus, Victor, Mathews, Carol, Lowe, Thomas, and Freimer, Nelson
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Adolescent ,Calcium-Binding Proteins ,Cell Adhesion Molecules ,Neuronal ,Child ,Collagen Type IX ,DNA Copy Number Variations ,Female ,Genetic Predisposition to Disease ,Genotype ,Humans ,Male ,Nerve Tissue Proteins ,Neural Cell Adhesion Molecules ,Polymorphism ,Single Nucleotide ,Tourette Syndrome - Abstract
Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.
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- 2013
9. Reconstructing Native American population history
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Reich, David, Patterson, Nick, Campbell, Desmond, Tandon, Arti, Mazieres, Stéphane, Ray, Nicolas, Parra, Maria V, Rojas, Winston, Duque, Constanza, Mesa, Natalia, García, Luis F, Triana, Omar, Blair, Silvia, Maestre, Amanda, Dib, Juan C, Bravi, Claudio M, Bailliet, Graciela, Corach, Daniel, Hünemeier, Tábita, Bortolini, Maria Cátira, Salzano, Francisco M, Petzl-Erler, María Luiza, Acuña-Alonzo, Victor, Aguilar-Salinas, Carlos, Canizales-Quinteros, Samuel, Tusié-Luna, Teresa, Riba, Laura, Rodríguez-Cruz, Maricela, Lopez-Alarcón, Mardia, Coral-Vazquez, Ramón, Canto-Cetina, Thelma, Silva-Zolezzi, Irma, Fernandez-Lopez, Juan Carlos, Contreras, Alejandra V, Jimenez-Sanchez, Gerardo, Gómez-Vázquez, Maria José, Molina, Julio, Carracedo, Ángel, Salas, Antonio, Gallo, Carla, Poletti, Giovanni, Witonsky, David B, Alkorta-Aranburu, Gorka, Sukernik, Rem I, Osipova, Ludmila, Fedorova, Sardana A, Vasquez, René, Villena, Mercedes, Moreau, Claudia, Barrantes, Ramiro, Pauls, David, Excoffier, Laurent, Bedoya, Gabriel, Rothhammer, Francisco, Dugoujon, Jean-Michel, Larrouy, Georges, Klitz, William, Labuda, Damian, Kidd, Judith, Kidd, Kenneth, Di Rienzo, Anna, Freimer, Nelson B, Price, Alkes L, and Ruiz-Linares, Andrés
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Biological Sciences ,Genetics ,History ,Heritage and Archaeology ,Human Society ,Historical Studies ,Anthropology ,American Indian or Alaska Native ,Americas ,Asia ,Cluster Analysis ,Emigration and Immigration ,Gene Flow ,Genetics ,Population ,History ,Ancient ,Humans ,Indians ,North American ,Models ,Genetic ,Phylogeny ,Polymorphism ,Single Nucleotide ,Siberia ,General Science & Technology - Abstract
The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.
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- 2012
10. Two subtypes of intervertebral disc degeneration distinguished by large-scale population-based study
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Li, Yan, Samartzis, Dino, Campbell, Desmond D., Cherny, Stacey S., Cheung, Kenneth M.C., Luk, Keith D.K., Karppinen, Jaro, Song, Youqiang, Cheah, Kathryn S., Chan, Danny, and Sham, Pak C.
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- 2016
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11. Gene Variants at Loci Related to Blood Pressure Account for Variation in Response to Antihypertensive Drugs Between Black and White Individuals: Genomic Precision Medicine May Dispense With Ethnicity
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Iniesta, Raquel, Campbell, Desmond, Venturini, Cristina, Faconti, Luca, Singh, Sonal, Irvin, Marguerite R., Cooper-DeHoff, Rhonda M., Johnson, Julie A., Turner, Stephen T., Arnett, Donna K., Weale, Michael E., Warren, Helen, Munroe, Patricia B., Cruickshank, Kennedy, Padmanabhan, Sandosh, Lewis, Cathryn, and Chowienczyk, Phil
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- 2019
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12. Biases Arising from Using Linked Administrative Data for Research: A Conceptual Framework from Registration to Analysis
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Shaw, Richard, Harron, Katie, Pescarini, Julia, Júnior, Elzo, Siroky, Andressa, Campbell, Desmond, Dundas, Ruth, Ichihara, Maria Yury, Barreto, Mauricio, and Katikireddi, Vittal
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Information Systems and Management ,Health Informatics ,Information Systems ,Demography - Abstract
Objectives:\ud Administrative data are primarily collected for operational processes and these processes can lead to sources of bias that may not be adequately considered by researchers. We provide a framework to help understand how biases might arise from using linked administrative data, and hopefully aid future study designs.\ud \ud \ud Approach:\ud We developed the conceptual framework based on the team’s experiences with the 100 Million Brazilian Cohort (100MCohort) which contains records of more than 131 million people whose families applied for social assistance between 2001 and 2018, linked to other administrative data sources. We provide examples from the 100MCohort of where and how in the linkage process different forms of bias could arise. We make recommendations on how biases might be addressed using commonly available external data.\ud \ud \ud Results:\ud The conceptual framework covers the whole data generating process from people and events occurring in the population through to deriving variables for analysis. The framework comprises three distinct stages: 1) Recording and registration of events in administrative systems such as Brazil’s Mortality Information System (SIM) and the Hospital Information System (SIH); 2) Linkage of different data sources, for example using exact matching via the Social Identification Number (NIS) in Brazil’s CadÚnico database or linkage algorithms; 3) Cleaning and coding data used both for analysis and linkage. The biases arising from linkage can be better understood by applying theory and making additional metadata available.\ud \ud \ud Conclusion:\ud Maximising the potential of administrative data for research requires a better understanding of how biases arise. This is best achieved by considering the entire data generating process, and better communication among all those involved in the data collection and linkage processes.
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- 2022
13. Impact of Brazil’s Bolsa Família Programme on cardiovascular and all-cause mortality: a natural experiment study using the 100 Million Brazilian Cohort
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Pescarini, Julia M, primary, Campbell, Desmond, additional, Amorim, Leila D, additional, Falcão, Ila R, additional, Ferreira, Andrêa J F, additional, Allik, Mirjam, additional, Shaw, Richard J, additional, Malta, Deborah C, additional, Ali, M Sanni, additional, Smeeth, Liam, additional, Barreto, Mauricio L, additional, Leyland, Alastair, additional, Craig, Peter, additional, Aquino, Estela M L, additional, and Katikireddi, Srinivasa Vittal, additional
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- 2022
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14. Comparing Anxiety and Depression in Information Technology Workers with Others in Employment: A UK Biobank Cohort Study
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Lalloo, Drushca, primary, Lewsey, Jim, additional, Katikireddi, Srinivasa Vittal, additional, Macdonald, Ewan B, additional, Campbell, Desmond, additional, and Demou, Evangelia, additional
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- 2022
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15. Cognitive impairment among children at-risk for schizophrenia
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Dickson, Hannah, Cullen, Alexis E., Reichenberg, Abraham, Hodgins, Sheilagh, Campbell, Desmond D., Morris, Robin G., and Laurens, Kristin R.
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- 2014
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16. Local True Discovery Rate Weighted Polygenic Scores Using GWAS Summary Data
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Mak, Timothy Shin Heng, Kwan, Johnny Sheung Him, Campbell, Desmond Dedalus, and Sham, Pak Chung
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- 2016
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17. Orbital Motion of Electrically Charged Spheres in Microgravity
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Banerjee, Shubho, Andring, Kevin, and Campbell, Desmond
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The similar mathematical forms of Coulomb's law and Newton's law of gravitation suggest that two uniformly charged spheres should be able to orbit each other just as two uniform spheres of mass are known to do. In this paper we describe an experiment that we performed to demonstrate such an orbit. This is the first published account of a successful orbit using electrostatic forces.
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- 2008
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18. Effects of depression on employment and social outcomes: a Mendelian randomisation study
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Campbell, Desmond, primary, Green, Michael James, additional, Davies, Neil, additional, Demou, Evangelia, additional, Howe, Laura D, additional, Harrison, Sean, additional, Smith, Daniel J, additional, Howard, David M, additional, McIntosh, Andrew M, additional, Munafò, Marcus, additional, and Katikireddi, Srinivasa Vittal, additional
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- 2022
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19. The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research
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Iyegbe, Conrad, Campbell, Desmond, Butler, Amy, Ajnakina, Olesya, and Sham, Pak
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- 2014
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20. Clinical burden, risk factor impact and outcomes following myocardial infarction and stroke: A 25-year individual patient level linkage study
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Shah, Anoop S.V., primary, Lee, Kuan Ken, additional, Pérez, Jesús Alberto Rodríguez, additional, Campbell, Desmond, additional, Astengo, Federica, additional, Logue, Jennifer, additional, Gallacher, Peter James, additional, Katikireddi, Srinivasa Vittal, additional, Bing, Rong, additional, Alam, Shirjel R., additional, Anand, Atul, additional, Sudlow, Catherine, additional, Fischbacher, Colin M, additional, Lewsey, Jim, additional, Perel, Pablo, additional, Newby, David E., additional, Mills, Nicholas L., additional, and McAllister, David A., additional
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- 2021
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21. Application of Haralick texture features in brain [18F]-florbetapir positron emission tomography without reference region normalization
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Campbell,Desmond L, Kang,Hakmook, and Shokouhi,Sepideh
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Aged, 80 and over ,Male ,Amyloid ,Aniline Compounds ,Brain ,Severity of Illness Index ,Pattern Recognition, Automated ,ROC Curve ,Alzheimer Disease ,Clinical Interventions in Aging ,Positron-Emission Tomography ,Disease Progression ,florbetapir ,Humans ,Cognitive Dysfunction ,Ethylene Glycols ,Female ,gray level co-occurrence matrix ,Haralick features ,entropy ,Original Research ,energy ,Aged - Abstract
DesmondL Campbell,1 Hakmook Kang,2 Sepideh Shokouhi1 On behalf of The Alzheimer’s Disease Neuroimaging Initiative 1Department of Radiology and Radiological Sciences, 2Department of Biostatistics, Vanderbilt University Medical Center, Vanderbilt University Institute of Imaging Science, Nashville, TN, USA Objectives: Semi-quantitative image analysis methods in Alzheimer’s Disease (AD) require normalization of positron emission tomography (PET) images. However, recent studies have found variabilities associated with reference region selection of amyloid PET images. Haralick features (HFs) generated from the Gray Level Co-occurrence Matrix (GLCM) quantify spatial characteristics of amyloid PET radiotracer uptake without the need for intensity normalization. The objective of this study is to calculate several HFs in different diagnostic groups and determine the group differences.Methods: All image and metadata were acquired through the Alzheimer’s Disease Neuroimaging Initiative database. Subjects were grouped in three ways: by clinical diagnosis, by APOE e4 allele, and by Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) score. Several GLCM matrices were calculated for different direction and distances (1–4 mm) from multiple regions on PET images. The HFs, contrast, correlation, dissimilarity, energy, entropy, and homogeneity, were calculated from these GLCMs. Wilcoxon tests and Student t-tests were performed on Haralick features and standardized uptake value ratio (SUVR) values, respectively, to determine group differences. In addition to statistical testing, receiver operating characteristic (ROC) curves were generated to determine the discrimination performance of the selected regional HFs and the SUVR values.Results: Preliminary results from statistical testing indicate that HFs were capable of distinguishing groups at baseline and follow-up (false discovery rate corrected p
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- 2017
22. Mental health and health behaviours before and during the initial phase of the COVID-19 lockdown: longitudinal analyses of the UK Household Longitudinal Study
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Niedzwiedz, Claire L, primary, Green, Michael James, additional, Benzeval, Michaela, additional, Campbell, Desmond, additional, Craig, Peter, additional, Demou, Evangelia, additional, Leyland, Alastair, additional, Pearce, Anna, additional, Thomson, Rachel, additional, Whitley, Elise, additional, and Katikireddi, Srinivasa Vittal, additional
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- 2020
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23. The causal effects of health conditions and risk factors on social and socioeconomic outcomes: Mendelian randomization in UK Biobank
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Harrison, Sean, primary, Davies, Alisha R, additional, Dickson, Matt, additional, Tyrrell, Jessica, additional, Green, Michael J, additional, Katikireddi, Srinivasa Vittal, additional, Campbell, Desmond, additional, Munafò, Marcus, additional, Dixon, Padraig, additional, Jones, Hayley E, additional, Rice, Frances, additional, Davies, Neil M, additional, and Howe, Laura D, additional
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- 2020
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24. Estimated effects of health conditions and risk factors on social and socioeconomic outcomes: mendelian randomisation of UK Biobank data
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Harrison, Sean, primary, Davies, Alisha R, additional, Dickson, Matt, additional, Tyrrell, Jessica, additional, Green, Michael J, additional, Katikireddi, Srinivasa Vittal, additional, Campbell, Desmond, additional, Munafò, Marcus, additional, Dixon, Padraig, additional, Jones, Hayley E, additional, Rice, Frances, additional, Davies, Neil M, additional, and Howe, Laura D, additional
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- 2019
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25. The Causal Effects of Health Conditions and Risk Factors on Social and Socioeconomic Outcomes: Mendelian Randomization in UK Biobank
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Harrison, Sean, primary, Davies, Alisha R, additional, Dickson, Matt, additional, Tyrrell, Jessica, additional, Green, Michael J, additional, Katikireddi, Srinivasa Vittal, additional, Campbell, Desmond, additional, Munafò, Marcus, additional, Dixon, Padraig, additional, Jones, Hayley E, additional, Rice, Frances, additional, Davies, Neil M, additional, and Howe, Laura D, additional
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- 2019
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26. Salt stress in the renal tubules is linked to TAL specific expression of uromodulin and an upregulation of heat shock genes
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Graham, Lesley A., Aman, Alisha, Campbell, Desmond D., Augley, Julian, Graham, Delyth, McBride, Martin W., Fraser, Niall J., Ferreri, Nicholas R., Dominiczak, Anna F., and Padmanabhan, Sandosh
- Abstract
Previously, our comprehensive cardiovascular characterisation study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesised at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod mice have significantly lower blood pressure than Umod mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed to delineate salt stress pathways in tubules isolated from Umod mice (a model of sodium retention) and Umod mice (a model of sodium depletion) ±300mOsmol sodium chloride (n=3 per group) performing RNA-Seq. In response to salt stress, the tubules of Umod mice displayed an up regulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, p=2.48e-12) and Hspa1b (Log2 fold change 4.05, p=2.48e-12). This response was absent in tubules of Umod mice. Interestingly, 7 of the genes discordantly expressed in the Umod tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress.
- Published
- 2018
27. Multifactorial disease risk calculator: risk prediction for multifactorial disease pedigrees
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Campbell, Desmond D., Li, Yiming, and Sham, Pak C.
- Abstract
Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported methodology based on a liability-threshold model. Multifactorial disease models incorporating all the following features in combination are handled: quantitative risk factors (including polygenic scores), categorical risk factors (including major genetic risk loci), stratified age of onset curves, and the partition of the population variance in disease liability into genetic, shared, and unique environment effects. It allows the application of such models to disease pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree members, (ii) n year risk for unaffected pedigree members, and (iii) the disease pedigree's joint liability distribution. Risk prediction for each pedigree member is based on using the constructed disease model to appropriately weigh evidence on disease risk available from personal attributes and family history. Evidence is used to construct the disease pedigree's joint liability distribution. From this, lifetime and n year risk can be predicted. Example disease models and pedigrees are provided at the website and are used in accompanying tutorials to illustrate the features available. The website is built on an R package which provides the functionality for pedigree validation, disease model construction, and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current.
- Published
- 2018
28. Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial
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Giovannini Caterina, Zobel Astrid, Strohmaier Jana, Jorgensen Lisbeth, Szczepankiewicz Aleksandra, Placentino Anna, Souery Daniel, Maier Wolfgang, Hauser Joanna, Henigsberg Neven, Mors Ole, Rietschel Marcella, Marusic Andrej, Uher Rudolf, Perroud Nader, Elkin Amanda, Gunasinghe Cerisse, Gray Joanna, Campbell Desmond, Gupta Bhanu, Farmer Anne E, McGuffin Peter, and Aitchison Katherine J
- Subjects
Medicine - Abstract
Abstract Background Suicidal thoughts and behaviours during antidepressant treatment, especially during the first weeks of treatment, have prompted warnings by regulatory bodies. The aim of the present study is to investigate the course and predictors of emergence and worsening of suicidal ideation during tricyclic antidepressant and serotonin reuptake inhibitor treatment. Methods In a multicentre part-randomised open-label study, 811 adult patients with moderate to severe unipolar depression were allocated to flexible dosage of escitalopram or nortriptyline for 12 weeks. The suicidality items of three standard measures were integrated in a suicidal ideation score. Increases in this score were classified as treatment emergent suicidal ideation (TESI) or treatment worsening suicidal ideation (TWOSI) according to the absence or presence of suicidal ideation at baseline. Results Suicidal ideation decreased during antidepressant treatment. Rates of TESI and TWOSI peaked in the fifth week. Severity of depression predicted TESI and TWOSI. In men, nortriptyline was associated with a 9.8-fold and 2.4-fold increase in TESI and TWOSI compared to escitalopram, respectively. Retirement and history of suicide attempts predicted TWOSI. Conclusion Increases in suicidal ideation were associated with depression severity and decreased during antidepressant treatment. In men, treatment with escitalopram is associated with lower risk of suicidal ideation compared to nortriptyline. Clinicians should remain alert to suicidal ideation beyond the initial weeks of antidepressant treatment. Trial registration EudraCT (No.2004-001723-38) and ISRCTN (No. 03693000).
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- 2009
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29. Mental health and health behaviours before and during the initial phase of the COVID-19 lockdown: longitudinal analyses of the UK Household Longitudinal Study.
- Author
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Niedzwiedz, Claire L., Green, Michael James, Benzeval, Michaela, Campbell, Desmond, Craig, Peter, Demou, Evangelia, Leyland, Alastair, Pearce, Anna, Thomson, Rachel, Whitley, Elise, and Katikireddi, Srinivasa Vittal
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ALCOHOLISM ,CONFIDENCE intervals ,PSYCHOLOGICAL distress ,HEALTH behavior ,INTERVIEWING ,LONELINESS ,LONGITUDINAL method ,MENTAL health ,QUESTIONNAIRES ,SMOKING ,SOCIOECONOMIC factors ,DISEASE prevalence ,CROSS-sectional method ,ELECTRONIC cigarettes ,DESCRIPTIVE statistics ,ATTITUDES toward illness ,STAY-at-home orders ,COVID-19 pandemic - Published
- 2021
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30. Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees
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Campbell, Desmond D, primary, Li, Yiming, additional, and Sham, Pak C, additional
- Published
- 2017
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31. The Social Work Task in an Acute Psychiatric In-Patient Unit
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McAULEY, PATRICIA, CATHERWOOD, MARY-LOUISE, BOLTON, ROSEMARY, and CAMPBELL, DESMOND
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- 1983
32. Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder:A Pilot Study
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Trotta, Antonella, Iyegbe, Conrad Osamede, Di Forti, Marta, Sham, Pak, Campbell, Desmond, Cherny, Stacey, Mondelli, Valeria, Aitchison, KJ, Murray, Robin MacGregor, Vassos, Evangelos, and Fisher, Helen
- Abstract
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis.
- Published
- 2016
33. Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study
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Trotta, Antonella, Iyegbe, Conrad, Di Forti, Marta, Sham, Pak C., Campbell, Desmond D., Cherny, Stacey S., Mondelli, Valeria, Aitchison, Katherine J., Murray, Robin M., Vassos, Evangelos, and Fisher, Helen L.
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Adult ,Male ,Multifactorial Inheritance ,Etiology ,Psychometrics ,lcsh:Medicine ,Social Sciences ,Pilot Projects ,Criminology ,Pathology and Laboratory Medicine ,Research and Analysis Methods ,Pediatrics ,Risk Assessment ,Young Adult ,Sociology ,Risk Factors ,Mental Health and Psychiatry ,Medicine and Health Sciences ,Genetics ,Psychology ,Humans ,Genetic Predisposition to Disease ,Child Abuse ,lcsh:Science ,Genome ,lcsh:R ,Psychoses ,Biology and Life Sciences ,Human Genetics ,Pilot Studies ,Adult Survivors of Child Adverse Events ,Psychotic Disorders ,Research Design ,Schizophrenia ,lcsh:Q ,Female ,Gene-Environment Interaction ,Crime ,Research Article - Abstract
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis.
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- 2016
34. A single nucleotide variant in HNF-1β is associated with maturity-onset diabetes of the young in a large Chinese family
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Zhou, Peng, Wei, Ran, Guo, Zhenkui, Zhu, Haining, Campbell, Desmond, Li, Qi, Xu, Xiaoqun, Wang, Junfu, Luan, Meng, Chen, Xing, and Chen, Gang
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Maturity-onset diabetes of the young (MODY) ,lcsh:Public aspects of medicine ,lcsh:RA1-1270 ,Maturity-onset diabetes of the young type 5 (MODY5) ,Hepatic nuclear factor 1 beta (HNF1β) - Abstract
Background:\ud \ud Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported.\ud \ud Methods:\ud \ud To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants.\ud \ud Results:\ud \ud Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P
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- 2016
35. Additional file 1: of Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes
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Wong, John, Campbell, Desmond, Ngo, Ngoc, Yeung, Fanny, Cheng, Guo, Tang, Clara, Chung, Patrick, Tran, Ngoc, Man-Ting So, Cherny, Stacey, Pak Sham, Tam, Paul, and Maria-Mercè Garcia-Barcelo
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Supplementary information. (DOC 653 kb)
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- 2016
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36. Additional file 1: of Sacral agenesis: a pilot whole exome sequencing and copy number study
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Porsch, Robert, Merello, Elisa, Marco, Patrizia De, Cheng, Guo, Rodriguez, Laura, Manting So, Pak Sham, Tam, Paul, Capra, Valeria, Cherny, Stacey, Maria-Mercè Garcia-Barcelo, and Campbell, Desmond
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Supplementary Methods and Material. (DOCX 51Â kb)
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- 2016
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37. Orbital motion of electrically charged spheres in microgravity
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Banerjee, Shubho, Andring, Kevin, Campbell, Desmond, Janeski, John, Keedy, Daniel, Quinn, Sean, and Hoffmeister, Brent
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Polarization (Electricity) -- Research ,Microgravity -- Research ,Sphere -- Analysis ,Electrostatic interactions -- Research ,Coulomb's law -- Analysis ,Education ,Physics - Published
- 2008
38. Molecular Breast Imaging Using Synthetic Projections From High-Purity Germanium Detectors: A Simulation Study
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Campbell, Desmond, primary and Peterson, Todd, additional
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- 2017
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39. 133. Interplay Between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study
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Trotta, Antonella, primary, Iyegbe, Conrad, additional, Di Forti, Marta, additional, Sham, Pak C, additional, Campbell, Desmond D, additional, Cherny, Stacey, additional, Mondelli, Valeria, additional, Aitchison, Katherine, additional, Murray, Robin, additional, Vassos, Evangelos, additional, and Fisher, Helen, additional
- Published
- 2017
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40. Sacral agenesis: a pilot whole exome sequencing and copy number study
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Porsch, Robert M., primary, Merello, Elisa, additional, De Marco, Patrizia, additional, Cheng, Guo, additional, Rodriguez, Laura, additional, So, Manting, additional, Sham, Pak C., additional, Tam, Paul K., additional, Capra, Valeria, additional, Cherny, Stacey S., additional, Garcia-Barcelo, Maria-Mercè, additional, and Campbell, Desmond D., additional
- Published
- 2016
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41. Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes
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Wong, John K. L., primary, Campbell, Desmond, additional, Ngo, Ngoc Diem, additional, Yeung, Fanny, additional, Cheng, Guo, additional, Tang, Clara S. M., additional, Chung, Patrick H. Y., additional, Tran, Ngoc Son, additional, So, Man-ting, additional, Cherny, Stacey S., additional, Sham, Pak C., additional, Tam, Paul K., additional, and Garcia-Barcelo, Maria-Mercè, additional
- Published
- 2016
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42. Peer review of 'The signed Kolmogorov-Smirnov test: why it should not be used'
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Campbell, Desmond
- Abstract
This is the open peer reviewers comments and recommendations regarding the submitted GigaScience article and/or dataset.
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- 2015
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43. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder
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Yu, Dongmei, Mathews, Carol A., Scharf, Jeremiah M., Neale, Benjamin M., Davis, Lea K., Gamazon, Eric R., Derks, Eske M., Evans, Patrick, Edlund, Christopher K., Crane, Jacquelyn, Fagerness, Jesen A., Osiecki, Lisa, Gallagher, Patience, Gerber, Gloria, Haddad, Stephen, Illmann, Cornelia, McGrath, Lauren M., Mayerfeld, Catherine, Arepalli, Sampath, Barlassina, Cristina, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrió, Gabriel Bedoya, Bienvenu, O. Joseph, Black, Donald, Bloch, Michael H., Brentani, Helena, Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond D., Cappi, Carolina, Cardona Silgado, Julio C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Cook, Edwin H., Cookson, M. R., Coric, Vladimir, Cullen, Bernadette, Cusi, Daniele, Delorme, Richard, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Grünblatt, Edna, Hardy, John, Heiman, Gary A., Hemmings, Sian M.J., Herrera, Luis D., Hezel, Dianne M., Hoekstra, Pieter J., Jankovic, Joseph, Kennedy, James L., King, Robert A., Konkashbaev, Anuar I., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L., Lupoli, Sara, Macciardi, Fabio, Maier, Wolfgang, Manunta, Paolo, Marconi, Maurizio, McCracken, James T., Mesa Restrepo, Sandra C., Moessner, Rainald, Moorjani, Priya, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias, Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosário, Maria C., Rosenberg, David, Ruhrmann, Stephan, Sabatti, Chiara, Salvi, Erika, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Service, Susan K., Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, Eric, Tischfield, Jay A., Turiel, Maurizio, Valencia Duarte, Ana V., Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Walkup, John, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R., Westenberg, Herman G.M., Yao, Yin, Hounie, Ana G., Miguel, Euripedes C., Nicolini, Humberto, Wagner, Michael, Ruiz-Linares, Andres, Cath, Danielle C., McMahon, William, Posthuma, Danielle, Oostra, Ben A., Nestadt, Gerald, Rouleau, Guy A., Purcell, Shaun, Jenike, Michael A., Heutink, Peter, Hanna, Gregory L., Conti, David V., Arnold, Paul D., Freimer, Nelson, Stewart, S. Evelyn, Knowles, James A., Cox, Nancy J., and Pauls, David L.
- Subjects
Adult ,Male ,Psychiatric Status Rating Scales ,Obsessive-Compulsive Disorder ,Comorbidity ,behavioral disciplines and activities ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Article ,mental disorders ,Humans ,Female ,Genome-Wide Association Study ,Tourette Syndrome - Abstract
Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
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- 2014
44. Partitioning the heritability of Tourette Syndrome and obsessive compulsive disorder reveals differences in genetic architecture
- Author
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Keller, Matthew C., Davis, Lea K., Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., Neale, Benjamin M., Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J., Bloch, Michael H., Blom, Rianne M., Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C., Cath, Danielle C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Conti, David V., Cook, Edwin H., Coric, Vladimir, Cullen, Bernadette A., Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K., Egberts, Karin, Falkai, Peter, Fernandez, Thomas V., Gallagher, Patience J., Garrido, Helena, Geller, Daniel, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A., Hemmings, Sian M. J., Hounie, Ana G., Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A., Kennedy, James L., King, Robert A., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L., Macciardi, Fabio, McCracken, James T., McGrath, Lauren M., Mesa Restrepo, Sandra C., Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Osiecki, Lisa, Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias J., Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosàrio, Maria C., Rosenberg, David, Rouleau, Guy A., Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, E., Tischfield, Jay A., Valencia Duarte, Ana V., Vallada, Homero, Van Nieuwerburgh, Filip, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R., Westenberg, Herman G. M., Shugart, Yin Yao, Miguel, Euripedes C., McMahon, William, Wagner, Michael, Nicolini, Humberto, Posthuma, Danielle, Hanna, Gregory L., Heutink, Peter, Denys, Damiaan, Arnold, Paul D., Oostra, Ben A., Nestadt, Gerald, Freimer, Nelson B., Pauls, David L., Wray, Naomi R., Stewart, S. Evelyn, Mathews, Carol A., Knowles, James A., Cox, Nancy J., and Scharf, Jeremiah M.
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Gilles ,Missing Heritability ,Autism ,Life Sciences ,Brain ,Neuropsychiatric Disorders ,Expression ,Social and Behavioral Sciences ,Tic Disorders ,Common Snps ,mental disorders ,Medicine and Health Sciences ,Complex Diseases ,Family - Abstract
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
- Published
- 2013
45. Application of Haralick texture features in brain [18F]-florbetapir positron emission tomography without reference region normalization.
- Author
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Campbell, Desmond L., Hakmook Kang, and Shokouhi, Sepideh
- Subjects
ALZHEIMER'S disease ,POSITRON emission tomography ,T-test (Statistics) - Abstract
Objectives: Semi-quantitative image analysis methods in Alzheimer's Disease (AD) require normalization of positron emission tomography (PET) images. However, recent studies have found variabilities associated with reference region selection of amyloid PET images. Haralick features (HFs) generated from the Gray Level Co-occurrence Matrix (GLCM) quantify spatial characteristics of amyloid PET radiotracer uptake without the need for intensity normalization. The objective of this study is to calculate several HFs in different diagnostic groups and determine the group differences. Methods: All image and metadata were acquired through the Alzheimer's Disease Neuroimaging Initiative database. Subjects were grouped in three ways: by clinical diagnosis, by APOE e4 allele, and by Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score. Several GLCM matrices were calculated for different direction and distances (1-4 mm) from multiple regions on PET images. The HFs, contrast, correlation, dissimilarity, energy, entropy, and homogeneity, were calculated from these GLCMs. Wilcoxon tests and Student t-tests were performed on Haralick features and standardized uptake value ratio (SUVR) values, respectively, to determine group differences. In addition to statistical testing, receiver operating characteristic (ROC) curves were generated to determine the discrimination performance of the selected regional HFs and the SUVR values. Results: Preliminary results from statistical testing indicate that HFs were capable of distinguishing groups at baseline and follow-up (false discovery rate corrected p<0.05) in particular regions at much higher occurrences than SUVR (81 of 252). Conversely, we observed nearly no significant differences between all groups within ROIs at baseline or follow-up utilizing SUVR. From the ROC analysis, we found that the Energy and Entropy offered the best performance to distinguish Normal versus mild cognitive impairment and ADAS-Cog negative versus ADAS-Cog positive groups. Conclusion: These results suggest that this technique could improve subject stratification in AD drug trials and help to evaluate the disease progression and treatment effects longitudinally without the disadvantages associated with intensity normalization. [ABSTRACT FROM AUTHOR]
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- 2017
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46. Cost effective assay choice for rare disease study designs
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Campbell, Desmond D, primary, Porsch, Robert M, additional, Cherny, Stacey S, additional, Capra, Valeria, additional, Merello, Elisa, additional, De Marco, Patrizia, additional, Sham, Pak C, additional, and Garcia-Barceló, Maria-Mercè, additional
- Published
- 2015
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47. Longitudinal Positron Emission Tomography in Preventive Alzheimer's Disease Drug Trials, Critical Barriers from Imaging Science Perspective.
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Shokouhi, Sepideh, Campbell, Desmond, Brill, Aaron B., and Gwirtsman, Harry E.
- Subjects
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ALZHEIMER'S disease , *POSITRON emission tomography , *PHARMACEUTICAL research , *DEMENTIA , *NUCLEAR medicine , *AMYLOID beta-protein - Abstract
Recent Alzheimer's trials have recruited cognitively normal people at risk for Alzheimer's dementia. Due to the lack of clinical symptoms in normal population, conventional clinical outcome measures are not suitable for these early trials. While several groups are developing new composite cognitive tests that could serve as potential outcome measures by detecting subtle cognitive changes in normal people, there is a need for longitudinal brain imaging techniques that can correlate with temporal changes in these new tests and provide additional objective measures of neuropathological changes in brain. Positron emission tomography (PET) is a nuclear medicine imaging procedure based on the measurement of annihilation photons after positron emission from radiolabeled molecules that allow tracking of biological processes in body, including the brain. PET is a well-established in vivo imaging modality in Alzheimer's disease diagnosis and research due to its capability of detecting abnormalities in three major hallmarks of this disease. These include (1) amyloid beta plaques; (2) neurofibrillary tau tangles and (3) decrease in neuronal activity due to loss of nerve cell connection and death. While semiquantitative PET imaging techniques are commonly used to set discrete cut-points to stratify abnormal levels of amyloid accumulation and neurodegeneration, they are suboptimal for detecting subtle longitudinal changes. In this study, we have identified and discussed four critical barriers in conventional longitudinal PET imaging that may be particularly relevant for early Alzheimer's disease studies. These include within and across subject heterogeneity of AD-affected brain regions, PET intensity normalization, neuronal compensations in early disease stages and cerebrovascular amyloid deposition. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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48. Erratum: Corrigendum: Reconstructing Native American population history
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Reich, David, primary, Patterson, Nick, additional, Campbell, Desmond, additional, Tandon, Arti, additional, Mazieres, Stéphane, additional, Ray, Nicolas, additional, Parra, Maria V., additional, Rojas, Winston, additional, Duque, Constanza, additional, Mesa, Natalia, additional, García, Luis F., additional, Triana, Omar, additional, Blair, Silvia, additional, Maestre, Amanda, additional, Dib, Juan C., additional, Bravi, Claudio M., additional, Bailliet, Graciela, additional, Corach, Daniel, additional, Hünemeier, Tábita, additional, Bortolini, Maria Cátira, additional, Salzano, Francisco M., additional, Petzl-Erler, María Luiza, additional, Acuña-Alonzo, Victor, additional, Aguilar-Salinas, Carlos, additional, Canizales-Quinteros, Samuel, additional, Tusié-Luna, Teresa, additional, Riba, Laura, additional, Rodríguez-Cruz, Maricela, additional, Lopez-Alarcón, Mardia, additional, Coral-Vazquez, Ramón, additional, Canto-Cetina, Thelma, additional, Silva-Zolezzi, Irma, additional, Fernandez-Lopez, Juan Carlos, additional, Contreras, Alejandra V., additional, Jimenez-Sanchez, Gerardo, additional, Gómez-Vázquez, Maria José, additional, Molina, Julio, additional, Carracedo, Ángel, additional, Salas, Antonio, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, B.Witonsky, David, additional, Alkorta-Aranburu, Gorka, additional, Sukernik, Rem I., additional, Osipova, Ludmila, additional, Fedorova, Sardana A., additional, Vasquez, René, additional, Villena, Mercedes, additional, Moreau, Claudia, additional, Barrantes, Ramiro, additional, Pauls, David, additional, Excoffier, Laurent, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Dugoujon, Jean-Michel, additional, Larrouy, Georges, additional, Klitz, William, additional, Labuda, Damian, additional, Kidd, Judith, additional, Kidd, Kenneth, additional, Di Rienzo, Anna, additional, Freimer, Nelson B., additional, Price, Alkes L., additional, and Ruiz-Linares, Andrés, additional
- Published
- 2012
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49. Simulations investigating the impact of depth-of-interaction in Nuclear Breast Imaging with a dedicated germanium gamma camera
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Campbell, Desmond L., primary and Peterson, Todd E., additional
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- 2012
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50. Amerind Ancestry, Socioeconomic Status and the Genetics of Type 2 Diabetes in a Colombian Population
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Campbell, Desmond D., primary, Parra, Maria V., additional, Duque, Constanza, additional, Gallego, Natalia, additional, Franco, Liliana, additional, Tandon, Arti, additional, Hünemeier, Tábita, additional, Bortolini, Cátira, additional, Villegas, Alberto, additional, Bedoya, Gabriel, additional, McCarthy, Mark I., additional, Price, Alkes, additional, Reich, David, additional, and Ruiz-Linares, Andrés, additional
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- 2012
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