25 results on '"Campbell, Desmond D."'
Search Results
2. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.
- Author
-
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
- Subjects
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.
- Published
- 2015
3. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.
- Author
-
Nag, Abhishek, Bochukova, Elena G, Kremeyer, Barbara, Campbell, Desmond D, Muller, Heike, Valencia-Duarte, Ana V, Cardona, Julio, Rivas, Isabel C, Mesa, Sandra C, Cuartas, Mauricio, Garcia, Jharley, Bedoya, Gabriel, Cornejo, William, Herrera, Luis D, Romero, Roxana, Fournier, Eduardo, Reus, Victor I, Lowe, Thomas L, Farooqi, I Sadaf, Tourette Syndrome Association International Consortium for Genetics, Mathews, Carol A, McGrath, Lauren M, Yu, Dongmei, Cook, Ed, Wang, Kai, Scharf, Jeremiah M, Pauls, David L, Freimer, Nelson B, Plagnol, Vincent, and Ruiz-Linares, Andrés
- Subjects
Tourette Syndrome Association International Consortium for Genetics ,Humans ,Tourette Syndrome ,Genetic Predisposition to Disease ,Calcium-Binding Proteins ,Cell Adhesion Molecules ,Neuronal ,Neural Cell Adhesion Molecules ,Nerve Tissue Proteins ,Collagen Type IX ,Genotype ,Polymorphism ,Single Nucleotide ,Adolescent ,Child ,Female ,Male ,DNA Copy Number Variations ,Neurodegenerative ,Mental Health ,Human Genome ,Genetics ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Schizophrenia ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,General Science & Technology - 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.
- Published
- 2013
4. Two subtypes of intervertebral disc degeneration distinguished by large-scale population-based study
- Author
-
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.
- Published
- 2016
- Full Text
- View/download PDF
5. Cognitive impairment among children at-risk for schizophrenia
- Author
-
Dickson, Hannah, Cullen, Alexis E., Reichenberg, Abraham, Hodgins, Sheilagh, Campbell, Desmond D., Morris, Robin G., and Laurens, Kristin R.
- Published
- 2014
- Full Text
- View/download PDF
6. 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
-
Niedzwiedz, Claire L, primary, Green, Michael J, additional, Benzeval, Michaela, additional, Campbell, Desmond D, additional, Craig, Peter, additional, Demou, Evangelia, additional, Leyland, Alastair H, additional, Pearce, Anna, additional, Thomson, Rachel M, additional, Whitley, Elise, additional, and Katikireddi, S Vittal, additional
- Published
- 2020
- Full Text
- View/download PDF
7. Salt stress in the renal tubules is linked to TAL specific expression of uromodulin and an upregulation of heat shock genes
- Author
-
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
8. Multifactorial disease risk calculator: risk prediction for multifactorial disease pedigrees
- Author
-
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
9. Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees
- Author
-
Campbell, Desmond D, primary, Li, Yiming, additional, and Sham, Pak C, additional
- Published
- 2017
- Full Text
- View/download PDF
10. Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study
- Author
-
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.
- Subjects
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.
- Published
- 2016
11. 133. Interplay Between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study
- Author
-
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
- Full Text
- View/download PDF
12. Sacral agenesis: a pilot whole exome sequencing and copy number study
- Author
-
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
- Full Text
- View/download PDF
13. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder
- Author
-
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.
- Published
- 2014
14. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD
- Author
-
Sub String Theory Cosmology and ElemPart, Leerstoel Hout, Experimental psychopathology, 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, 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 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 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, Nurmi, Erika, 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, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R, Westenberg, Herman G M, Shugart, Yin Yao, 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 B, Stewart, S Evelyn, Knowles, James A, Cox, Nancy J, Pauls, David L, Sub String Theory Cosmology and ElemPart, Leerstoel Hout, Experimental psychopathology, 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, 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 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 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, Nurmi, Erika, 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, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R, Westenberg, Herman G M, Shugart, Yin Yao, 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 B, Stewart, S Evelyn, Knowles, James A, Cox, Nancy J, and Pauls, David L
- Published
- 2015
15. Cost effective assay choice for rare disease study designs
- Author
-
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
- Full Text
- View/download PDF
16. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations
- Author
-
van Os, Jim, Rutten, Bart P., Myin-Germeys, Inez, Delespaul, Philippe, Viechtbauer, Wolfgang, van Zelst, Catherine, Bruggeman, Richard, Reininghaus, Ulrich, Morgan, Craig, Murray, Robin M., Di Forti, Marta, McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., Gayer-Anderson, Charlotte, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Onyejiaka, Adanna, Bourque, Francois, Modinos, Gemma, Tognin, Stefania, Calem, Maria, O'Donovan, Michael C., Owen, Michael J., Holmans, Peter, Williams, Nigel, Craddock, Nicholas, Richards, Alexander, Humphreys, Isla, Meyer-Lindenberg, Andreas, Leweke, F. Markus, Tost, Heike, Akdeniz, Ceren, Rohleder, Cathrin, Bumb, J. Malte, Schwarz, Emanuel, Alptekin, Koksal, Ucok, Alp, Saka, Meram Can, Atbasoglu, E. Cem, Guloksuz, Sinan, Gumus-Akay, Guvem, Cihan, Burin, Karadag, Hasan, Soygur, Haldan, Cankurtaran, Eylem Sahin, Ulusoy, Semra, Akdede, Berna, Binbay, Tolga, Ayer, Ahmet, Noyan, Handan, Karadayi, Gulsah, Akturan, Elin, Ulas, Halis, Arango, Celso, Parellada, Mara, Bernardo, Miguel, Sanjuan, Julio, Bobes, Julio, Arrojo, Manuel, Luis Santos, Jose, Cuadrado, Pedro, Rodriguez Solano, Jose Juan, Carracedo, Angel, Garcia Bernardo, Enrique, Roldan, Laura, Lopez, Gonzalo, Cabrera, Bibiana, Cruz, Sabrina, Diaz Mesa, Eva Ma, Pouso, Maria, Jimenez, Estela, Sanchez, Teresa, Rapado, Marta, Gonzalez, Emiliano, Martinez, Covadonga, Sanchez, Emilio, Soledad Olmeda, Ma, de Haan, Lieuwe, Velthorst, Eva, van der Gaag, Mark, Selten, Jean-Paul, van Dam, Daniella, van der Ven, Elsje, van der Meer, Floor, Messchaert, Elles, Kraan, Tamar, Burger, Nadine, Leboyer, Marion, Szoke, Andrei, Schurhoff, Franck, Llorca, Pierre-Michel, Jamain, Stephane, Tortelli, Andrea, Frijda, Flora, Vilain, Jeanne, Galliot, Anne-Marie, Baudin, Gregoire, Ferchiou, Aziz, Richard, Jean-Romain, Bulzacka, Ewa, Charpeaud, Thomas, Tronche, Anne-Marie, De Hert, Marc, van Winkel, Ruud, Decoster, Jeroen, Derom, Catherine, Thiery, Evert, Stefanis, Nikos C., Sachs, Gabriele, Aschauer, Harald, Lasser, Iris, Winklbaur, Bernadette, Schlogelhofer, Monika, Riecher-Rossler, Anita, Borgwardt, Stefan, Walter, Anna, Harrisberger, Fabienne, Smieskova, Renata, Rapp, Charlotte, Ittig, Sarah, Soguel-Dit-Piquard, Fabienne, Studerus, Erich, Klosterkotter, Joachim, Ruhrmann, Stephan, Paruch, Julia, Julkowski, Dominika, Hilboll, Desiree, Sham, Pak C., Cherny, Stacey S., Chen, Eric Y. H., Campbell, Desmond D., Li, Miaoxin, Maria Romeo-Casabona, Carlos, Emaldi Cirion, Aitziber, Urruela Mora, Asier, Jones, Peter, Kirkbride, James, Cannon, Mary, Rujescu, Dan, Tarricone, Ilaria, Berardi, Domenico, Bonora, Elena, Seri, Marco, Marcacci, Thomas, Chiri, Luigi, Chierzi, Federico, Storbini, Viviana, Braca, Mauro, Minenna, Maria Gabriella, Donegani, Ivonne, Fioritti, Angelo, La Barbera, Daniele, La Cascia, Caterina Erika, Mule, Alice, Sideli, Lucia, Sartorio, Rachele, Ferraro, Laura, Tripoli, Giada, Seminerio, Fabio, Marinaro, Anna Maria, McGorry, Patrick, Nelson, Barnaby, Amminger, G. Paul, Pantelis, Christos, Menezes, Paulo R., Del-Ben, Cristina M., Tenan, Silvia H. Gallo, Shuhama, Rosana, Ruggeri, Mirella, Tosato, Sarah, Lasalvia, Antonio, Bonetto, Chiara, Ira, Elisa, Nordentoft, Merete, Krebs, Marie-Odile, Barrantes-Vidal, Neus, Cristobal, Paula, Kwapil, Thomas R., Brietzke, Elisa, Bressan, Rodrigo A., Gadelha, Ary, Maric, Nadja P., Andric, Sanja, Mihaljevic, Marina, Mirjanic, Tijana, van Os, Jim, Rutten, Bart P., Myin-Germeys, Inez, Delespaul, Philippe, Viechtbauer, Wolfgang, van Zelst, Catherine, Bruggeman, Richard, Reininghaus, Ulrich, Morgan, Craig, Murray, Robin M., Di Forti, Marta, McGuire, Philip, Valmaggia, Lucia R., Kempton, Matthew J., Gayer-Anderson, Charlotte, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Onyejiaka, Adanna, Bourque, Francois, Modinos, Gemma, Tognin, Stefania, Calem, Maria, O'Donovan, Michael C., Owen, Michael J., Holmans, Peter, Williams, Nigel, Craddock, Nicholas, Richards, Alexander, Humphreys, Isla, Meyer-Lindenberg, Andreas, Leweke, F. Markus, Tost, Heike, Akdeniz, Ceren, Rohleder, Cathrin, Bumb, J. Malte, Schwarz, Emanuel, Alptekin, Koksal, Ucok, Alp, Saka, Meram Can, Atbasoglu, E. Cem, Guloksuz, Sinan, Gumus-Akay, Guvem, Cihan, Burin, Karadag, Hasan, Soygur, Haldan, Cankurtaran, Eylem Sahin, Ulusoy, Semra, Akdede, Berna, Binbay, Tolga, Ayer, Ahmet, Noyan, Handan, Karadayi, Gulsah, Akturan, Elin, Ulas, Halis, Arango, Celso, Parellada, Mara, Bernardo, Miguel, Sanjuan, Julio, Bobes, Julio, Arrojo, Manuel, Luis Santos, Jose, Cuadrado, Pedro, Rodriguez Solano, Jose Juan, Carracedo, Angel, Garcia Bernardo, Enrique, Roldan, Laura, Lopez, Gonzalo, Cabrera, Bibiana, Cruz, Sabrina, Diaz Mesa, Eva Ma, Pouso, Maria, Jimenez, Estela, Sanchez, Teresa, Rapado, Marta, Gonzalez, Emiliano, Martinez, Covadonga, Sanchez, Emilio, Soledad Olmeda, Ma, de Haan, Lieuwe, Velthorst, Eva, van der Gaag, Mark, Selten, Jean-Paul, van Dam, Daniella, van der Ven, Elsje, van der Meer, Floor, Messchaert, Elles, Kraan, Tamar, Burger, Nadine, Leboyer, Marion, Szoke, Andrei, Schurhoff, Franck, Llorca, Pierre-Michel, Jamain, Stephane, Tortelli, Andrea, Frijda, Flora, Vilain, Jeanne, Galliot, Anne-Marie, Baudin, Gregoire, Ferchiou, Aziz, Richard, Jean-Romain, Bulzacka, Ewa, Charpeaud, Thomas, Tronche, Anne-Marie, De Hert, Marc, van Winkel, Ruud, Decoster, Jeroen, Derom, Catherine, Thiery, Evert, Stefanis, Nikos C., Sachs, Gabriele, Aschauer, Harald, Lasser, Iris, Winklbaur, Bernadette, Schlogelhofer, Monika, Riecher-Rossler, Anita, Borgwardt, Stefan, Walter, Anna, Harrisberger, Fabienne, Smieskova, Renata, Rapp, Charlotte, Ittig, Sarah, Soguel-Dit-Piquard, Fabienne, Studerus, Erich, Klosterkotter, Joachim, Ruhrmann, Stephan, Paruch, Julia, Julkowski, Dominika, Hilboll, Desiree, Sham, Pak C., Cherny, Stacey S., Chen, Eric Y. H., Campbell, Desmond D., Li, Miaoxin, Maria Romeo-Casabona, Carlos, Emaldi Cirion, Aitziber, Urruela Mora, Asier, Jones, Peter, Kirkbride, James, Cannon, Mary, Rujescu, Dan, Tarricone, Ilaria, Berardi, Domenico, Bonora, Elena, Seri, Marco, Marcacci, Thomas, Chiri, Luigi, Chierzi, Federico, Storbini, Viviana, Braca, Mauro, Minenna, Maria Gabriella, Donegani, Ivonne, Fioritti, Angelo, La Barbera, Daniele, La Cascia, Caterina Erika, Mule, Alice, Sideli, Lucia, Sartorio, Rachele, Ferraro, Laura, Tripoli, Giada, Seminerio, Fabio, Marinaro, Anna Maria, McGorry, Patrick, Nelson, Barnaby, Amminger, G. Paul, Pantelis, Christos, Menezes, Paulo R., Del-Ben, Cristina M., Tenan, Silvia H. Gallo, Shuhama, Rosana, Ruggeri, Mirella, Tosato, Sarah, Lasalvia, Antonio, Bonetto, Chiara, Ira, Elisa, Nordentoft, Merete, Krebs, Marie-Odile, Barrantes-Vidal, Neus, Cristobal, Paula, Kwapil, Thomas R., Brietzke, Elisa, Bressan, Rodrigo A., Gadelha, Ary, Maric, Nadja P., Andric, Sanja, Mihaljevic, Marina, and Mirjanic, Tijana
- Abstract
Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.
- Published
- 2014
17. Software for generating liability distributions for pedigrees conditional on their observed disease states and covariates
- Author
-
Campbell, Desmond D., Sham, Pak C., Knight, Jo, Wickham, Harvey, Landau, Sabine, Campbell, Desmond D., Sham, Pak C., Knight, Jo, Wickham, Harvey, and Landau, Sabine
- Abstract
For many multifactorial diseases, aetiology is poorly understood. A major research aim is the identification of disease predictors (environmental, biological, and genetic markers). In order to achieve this, a two-stage approach is proposed. The initial or synthesis stage combines observed pedigree data with previous genetic epidemiological research findings, to produce estimates of pedigree members' disease risk and predictions of their disease liability. A further analysis stage uses the latter as inputs to look for associations with potential disease markers. The incorporation of previous research findings into an analysis should lead to power gains. It also allows separate predictions for environmental and genetic liabilities to be generated. This should increase power for detecting disease predictors that are environmental or genetic in nature. Finally, the approach brings pragmatic benefits in terms of data reduction and synthesis, improving comprehensibility, and facilitating the use of existing statistical genetics tools. In this article we present a statistical model and Gibbs sampling approach to generate liability predictions for multifactorial disease for the synthesis stage. We have implemented the approach in a software program. We apply this program to a specimen disease pedigree, and discuss the results produced, comparing its results with those generated under a more naïve model. We also detail simulation studies that validate the software's operation.
- Published
- 2010
18. Amerind Ancestry, Socioeconomic Status and the Genetics of Type 2 Diabetes in a Colombian Population
- Author
-
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
- Published
- 2012
- Full Text
- View/download PDF
19. Software for generating liability distributions for pedigrees conditional on their observed disease states and covariates
- Author
-
Campbell, Desmond D., primary, Sham, Pak C., additional, Knight, Jo, additional, Wickham, Harvey, additional, and Landau, Sabine, additional
- Published
- 2009
- Full Text
- View/download PDF
20. CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1.
- Author
-
Nag, Abhishek, Bochukova, Elena G., Kremeyer, Barbara, Campbell, Desmond D., Muller, Heike, Valencia-Duarte, Ana V., Cardona, Julio, Rivas, Isabel C., Mesa, Sandra C., Cuartas, Mauricio, Garcia, Jharley, Bedoya, Gabriel, Cornejo, William, Herrera, Luis D., Romero, Roxana, Fournier, Eduardo, Reus, Victor I., Lowe, Thomas L., Farooqi, I. Sadaf, and Mathews, Carol A.
- Subjects
TOURETTE syndrome ,NEUROBEHAVIORAL disorders ,GENE rearrangement ,NEURODEVELOPMENTAL treatment ,GENE amplification ,GENETIC mutation ,ETIOLOGY of diseases ,SINGLE nucleotide polymorphisms - 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 ∼400kb 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
21. CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1.
- Author
-
Nag, Abhishek, Bochukova, Elena G., Kremeyer, Barbara, Campbell, Desmond D., Muller, Heike, Valencia-Duarte, Ana V., Cardona, Julio, Rivas, Isabel C., Mesa, Sandra C., Cuartas, Mauricio, Garcia, Jharley, Bedoya, Gabriel, Cornejo, William, Herrera, Luis D., Romero, Roxana, Fournier, Eduardo, Reus, Victor I., Lowe, Thomas L., Farooqi, I. Sadaf, and Mathews, Carol A.
- Subjects
- *
TOURETTE syndrome , *NEUROBEHAVIORAL disorders , *GENE rearrangement , *NEURODEVELOPMENTAL treatment , *GENE amplification , *GENETIC mutation , *ETIOLOGY of diseases , *SINGLE nucleotide polymorphisms - 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 ∼400kb 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
22. Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.
- Author
-
Graham LA, Aman A, Campbell DD, Augley J, Graham D, McBride MW, Fraser NJ, Ferreri NR, Dominiczak AF, and Padmanabhan S
- Subjects
- Animals, Gene Expression Regulation, HSP70 Heat-Shock Proteins genetics, Loop of Henle physiology, Male, Mice, Mutant Strains, Up-Regulation, Heat-Shock Response genetics, Kidney Tubules physiology, Salt Stress genetics, Uromodulin genetics
- Abstract
Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized 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 use RNA-Seq to delineate salt stress pathways in tubules isolated from Umod+/+ mice (a model of sodium retention) and Umod-/- mice (a model of sodium depletion) ± 300 mosmol sodium chloride ( n = 3 per group). In response to salt stress, the tubules of Umod+/+ mice displayed an upregulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, P = 2.48 e-12 ) and Hspa1b (Log2 fold change 4.05, P = 2.48 e-12 ). This response was absent in tubules of Umod-/- mice. Interestingly, seven 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
- Full Text
- View/download PDF
23. Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.
- Author
-
Campbell DD, Li Y, and Sham PC
- Subjects
- Humans, Internet, Models, Genetic, Reproducibility of Results, Risk Factors, Software, Disease genetics, Genetic Predisposition to Disease genetics, Multifactorial Inheritance genetics, Pedigree
- 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., (© 2017 WILEY PERIODICALS, INC.)
- Published
- 2018
- Full Text
- View/download PDF
24. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.
- Author
-
van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, and Mirjanic T
- Subjects
- Genetic Predisposition to Disease, Humans, Schizophrenia epidemiology, Social Environment, Gene-Environment Interaction, Schizophrenia genetics, Schizophrenic Psychology
- Abstract
Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF
25. Software for generating liability distributions for pedigrees conditional on their observed disease states and covariates.
- Author
-
Campbell DD, Sham PC, Knight J, Wickham H, and Landau S
- Subjects
- Depression genetics, Genetic Markers, Humans, Models, Statistical, Predictive Value of Tests, Probability, Risk Assessment, Software Validation, Genetic Predisposition to Disease genetics, Models, Genetic, Pedigree, Software
- Abstract
For many multifactorial diseases, aetiology is poorly understood. A major research aim is the identification of disease predictors (environmental, biological, and genetic markers). In order to achieve this, a two-stage approach is proposed. The initial or synthesis stage combines observed pedigree data with previous genetic epidemiological research findings, to produce estimates of pedigree members' disease risk and predictions of their disease liability. A further analysis stage uses the latter as inputs to look for associations with potential disease markers. The incorporation of previous research findings into an analysis should lead to power gains. It also allows separate predictions for environmental and genetic liabilities to be generated. This should increase power for detecting disease predictors that are environmental or genetic in nature. Finally, the approach brings pragmatic benefits in terms of data reduction and synthesis, improving comprehensibility, and facilitating the use of existing statistical genetics tools. In this article we present a statistical model and Gibbs sampling approach to generate liability predictions for multifactorial disease for the synthesis stage. We have implemented the approach in a software program. We apply this program to a specimen disease pedigree, and discuss the results produced, comparing its results with those generated under a more naïve model. We also detail simulation studies that validate the software's operation., (2009 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.