Search

Your search keyword '"Bass, Nicholas"' showing total 15 results
Start Over Author "Bass, Nicholas" Language undetermined
15 results on '"Bass, Nicholas"'

1. Rare coding variants in ten genes confer substantial risk for schizophrenia

Author

Singh, Tarjinder, Poterba, Timothy, Curtis, David, Akil, Huda, Al Eissa, Mariam, Barchas, Jack D, Bass, Nicholas, Bigdeli, Tim B, Breen, Gerome, Bromet, Evelyn J, Buckley, Peter F, Bunney, William E, Bybjerg-Grauholm, Jonas, Byerley, William F, Chapman, Sinéad B, Chen, Wei J, Churchhouse, Claire, Craddock, Nicholas, Cusick, Caroline M, DeLisi, Lynn, Dodge, Sheila, Escamilla, Michael A, Eskelinen, Saana, Fanous, Ayman H, Faraone, Stephen V, Fiorentino, Alessia, Francioli, Laurent, Gabriel, Stacey B, Gage, Diane, Gagliano Taliun, Sarah A, Ganna, Andrea, Genovese, Giulio, Glahn, David C, Grove, Jakob, Hall, Mei-Hua, Hämäläinen, Eija, Heyne, Henrike O, Holi, Matti, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Hwu, Hai-Gwo, Kahn, René S, Kang, Hyun Min, Karczewski, Konrad J, Kirov, George, Knowles, James A, Lee, Francis S, Lehrer, Douglas S, Lescai, Francesco, Malaspina, Dolores, Marder, Stephen R, McCarroll, Steven A, McIntosh, Andrew M, Medeiros, Helena, Milani, Lili, Morley, Christopher P, Morris, Derek W, Mortensen, Preben Bo, Myers, Richard M, Nordentoft, Merete, O'Brien, Niamh L, Olivares, Ana Maria, Ongur, Dost, Ouwehand, Willem H, Palmer, Duncan S, Paunio, Tiina, Quested, Digby, Rapaport, Mark H, Rees, Elliott, Rollins, Brandi, Satterstrom, F Kyle, Schatzberg, Alan, Scolnick, Edward, Scott, Laura J, Sharp, Sally I, Sklar, Pamela, Smoller, Jordan W, Sobell, Janet L, Solomonson, Matthew, Stahl, Eli A, Stevens, Christine R, Suvisaari, Jaana, Tiao, Grace, Watson, Stanley J, Watts, Nicholas A, Blackwood, Douglas H, Børglum, Anders D, Cohen, Bruce M, Corvin, Aiden P, Esko, Tõnu, Freimer, Nelson B, Glatt, Stephen J, Hultman, Christina M, McQuillin, Andrew, Palotie, Aarno, Pato, Carlos N, Pato, Michele T, Pulver, Ann E, and St Clair, David

Subjects
General Science & Technology, Human Genome, Neurosciences, Serious Mental Illness, Brain Disorders, Mental Health, Neurodevelopmental Disorders, Case-Control Studies, Receptors, Mutation, Neurological, Schizophrenia, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Exome, Aetiology, N-Methyl-D-Aspartate, Biotechnology
Abstract

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P

Published
2022

2. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Mullins, Niamh, Kang, JooEun, Campos, Adrian I, Coleman, Jonathan RI, Edwards, Alexis C, Galfalvy, Hanga, Levey, Daniel F, Lori, Adriana, Shabalin, Andrey, Starnawska, Anna, Su, Mei-Hsin, Watson, Hunna J, Adams, Mark, Awasthi, Swapnil, Gandal, Michael, Hafferty, Jonathan D, Hishimoto, Akitoyo, Kim, Minsoo, Okazaki, Satoshi, Otsuka, Ikuo, Ripke, Stephan, Ware, Erin B, Bergen, Andrew W, Berrettini, Wade H, Bohus, Martin, Brandt, Harry, Chang, Xiao, Chen, Wei J, Chen, Hsi-Chung, Crawford, Steven, Crow, Scott, DiBlasi, Emily, Duriez, Philibert, Fernández-Aranda, Fernando, Fichter, Manfred M, Gallinger, Steven, Glatt, Stephen J, Gorwood, Philip, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A, Hwu, Hai-Gwo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Keel, Pamela K, Kennedy, James L, Klump, Kelly L, Li, Dong, Liao, Shih-Cheng, Lieb, Klaus, Lilenfeld, Lisa, Liu, Chih-Min, Magistretti, Pierre J, Marshall, Christian R, Mitchell, James E, Monson, Eric T, Myers, Richard M, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W, Schmahl, Christian, Sokolowski, Marcus, Strober, Michael, Thornton, Laura M, Treasure, Janet, Tsuang, Ming T, Witt, Stephanie H, Woodside, D Blake, Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Air, Tracy M, Alda, Martin, Alfredsson, Lars, Andreassen, Ole A, Anjorin, Adebayo, Appadurai, Vivek, Soler Artigas, María, Van der Auwera, Sandra, Azevedo, M Helena, Bass, Nicholas, Bau, Claiton HD, Baune, Bernhard T, Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M, Bigdeli, Tim B, Binder, Elisabeth B, Boehnke, Michael, Boks, Marco P, Bosch, Rosa, and Braff, David L

Subjects
Genetic correlation, Genome-wide association study, Medical and Health Sciences, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Risk Factors, Polygenicity, Behavioral and Social Science, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Suicide attempt, Genetics, German Borderline Genomics Consortium, Humans, 2.1 Biological and endogenous factors, Polymorphism, Aetiology, Attempted, Pleiotropy, Psychiatry, Depressive Disorder, MVP Suicide Exemplar Workgroup, Mental Disorders, Prevention, Human Genome, Psychology and Cognitive Sciences, Major, Single Nucleotide, Biological Sciences, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Brain Disorders, Suicide, Mental Health, Good Health and Well Being, VA Million Veteran Program
Abstract

BackgroundSuicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.MethodsWe conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.ResultsTwo loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.ConclusionsOur results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Published
2022

3. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author

Blokland, Gabriëlla AM, Grove, Jakob, Chen, Chia-Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Schizophrenia Working Group of the Psychiatric Genomics Consortium, St Clair, David, Lencz, Todd, Mowry, Bryan J, Periyasamy, Sathish, Cairns, Murray J, Tooney, Paul A, Wu, Jing Qin, Kelly, Brian, Kirov, George, Sullivan, Patrick F, Corvin, Aiden, Riley, Brien P, Esko, Tõnu, Milani, Lili, Jönsson, Erik G, Palotie, Aarno, Ehrenreich, Hannelore, Begemann, Martin, Steixner-Kumar, Agnes, Sham, Pak C, Iwata, Nakao, Weinberger, Daniel R, Gejman, Pablo V, Sanders, Alan R, Buxbaum, Joseph D, Rujescu, Dan, Giegling, Ina, Konte, Bettina, Hartmann, Annette M, Bramon, Elvira, Murray, Robin M, Pato, Michele T, Lee, Jimmy, Melle, Ingrid, Molden, Espen, Ophoff, Roel A, McQuillin, Andrew, Bass, Nicholas J, Adolfsson, Rolf, Malhotra, Anil K, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Martin, Nicholas G, Fullerton, Janice M, Mitchell, Philip B, Schofield, Peter R, Forstner, Andreas J, Degenhardt, Franziska, Schaupp, Sabrina, Comes, Ashley L, Kogevinas, Manolis, Guzman-Parra, José, Reif, Andreas, Streit, Fabian, Sirignano, Lea, Cichon, Sven, Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Lissowska, Jolanta, Mayoral, Fermin, Müller-Myhsok, Bertram, Świątkowska, Beata, Schulze, Thomas G, Nöthen, Markus M, Rietschel, Marcella, Kelsoe, John, Leboyer, Marion, Jamain, Stéphane, Etain, Bruno, Bellivier, Frank, Vincent, John B, Alda, Martin, O'Donovan, Claire, Cervantes, Pablo, Biernacka, Joanna M, Frye, Mark, McElroy, Susan L, Scott, Laura J, Stahl, Eli A, Landén, Mikael, Hamshere, Marian L, Smeland, Olav B, Djurovic, Srdjan, Vaaler, Arne E, Andreassen, Ole A, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Baune, Bernhard T, Air, Tracy, Preisig, Martin, Uher, Rudolf, Levinson, Douglas F, Weissman, Myrna M, Potash, James B, and Shi, Jianxin

Subjects
Male, Genome-wide association study, Bipolar Disorder, iPSYCH, Major depressive disorder, Medical and Health Sciences, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Receptors, Sex differences, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, Polymorphism, Aetiology, Genotype-by-sex interaction, Psychiatry, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Depressive Disorder, Sex Characteristics, Vascular Endothelial Growth Factor, Human Genome, Psychology and Cognitive Sciences, Neurosciences, Endothelial Cells, Major, Single Nucleotide, Biological Sciences, Serious Mental Illness, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Brain Disorders, Mental Health, Psychotic Disorders, Sulfurtransferases, Schizophrenia, Female, Biotechnology
Abstract

BackgroundSex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.MethodsWe conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.ResultsAcross disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p= 3.2× 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1× 10-6) for cross-disorder G×S interaction (rs7302529, p= 1.6× 10-7; rs73033497, p= 8.8× 10-7; rs7914279, p= 6.4× 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p= 8.97× 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p= 1.5× 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p= 1.1× 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).ConclusionsIn the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Published
2022

4. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Mullins, Niamh, Forstner, Andreas J, O'Connell, Kevin S, Coombes, Brandon, Coleman, Jonathan RI, Qiao, Zhen, Als, Thomas D, Bigdeli, Tim B, Børte, Sigrid, Bryois, Julien, Charney, Alexander W, Drange, Ole Kristian, Gandal, Michael J, Hagenaars, Saskia P, Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M, Sloofman, Laura G, Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S, Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C, Bergen, Sarah E, Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P, Bosch, Rosa, Brum, Murielle, Brumpton, Ben M, Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M, Dale, Anders M, Dalkner, Nina, David, Friederike S, Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L, Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I Nicol, Fiorentino, Alessia, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R, Gordon, Scott D, Gordon-Smith, Katherine, Greenwood, Tiffany A, Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Kalman, Janos L

Subjects
Multifactorial Inheritance, Bipolar Disorder, Quantitative Trait Loci, Medical and Health Sciences, Chromosomes, Major Histocompatibility Complex, Risk Factors, HUNT All-In Psychiatry, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Aetiology, Genome, Human Genome, Neurosciences, Biological Sciences, Serious Mental Illness, Brain Disorders, Phenotype, Mental Health, Good Health and Well Being, Case-Control Studies, Neurological, Human, Genome-Wide Association Study, Biotechnology, Developmental Biology
Abstract

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2021

5. GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

Author

Mullins, Niamh, Bigdeli, Tim B, Børglum, Anders D, Coleman, Jonathan RI, Demontis, Ditte, Mehta, Divya, Power, Robert A, Ripke, Stephan, Stahl, Eli A, Starnawska, Anna, Anjorin, Adebayo, M.R.C.Psych, Corvin, Aiden, Sanders, Alan R, Forstner, Andreas J, Reif, Andreas, Koller, Anna C, Świątkowska, Beata, Baune, Bernhard T, Müller-Myhsok, Bertram, Penninx, Brenda WJH, Pato, Carlos, Zai, Clement, Rujescu, Dan, Hougaard, David M, Quested, Digby, Levinson, Douglas F, Binder, Elisabeth B, Byrne, Enda M, Agerbo, Esben, Dr.Med.Sc, Streit, Fabian, Mayoral, Fermin, Bellivier, Frank, Degenhardt, Franziska, Breen, Gerome, Morken, Gunnar, Turecki, Gustavo, Rouleau, Guy A, Grabe, Hans J, Völzke, Henry, Jones, Ian, Giegling, Ina, Agartz, Ingrid, Melle, Ingrid, Lawrence, Jacob, Walters, James TR, Strohmaier, Jana, Shi, Jianxin, Hauser, Joanna, Biernacka, Joanna M, Vincent, John B, Kelsoe, John, Strauss, John S, Lissowska, Jolanta, Pimm, Jonathan, Smoller, Jordan W, Guzman-Parra, José, Berger, Klaus, Scott, Laura J, Jones, Lisa A, Azevedo, M Helena, Trzaskowski, Maciej, Kogevinas, Manolis, Rietschel, Marcella, Boks, Marco, Ising, Marcus, Grigoroiu-Serbanescu, Maria, Hamshere, Marian L, Leboyer, Marion, Frye, Mark, Nöthen, Markus M, Alda, Martin, Preisig, Martin, Nordentoft, Merete, Boehnke, Michael, O'Donovan, Michael C, Owen, Michael J, Pato, Michele T, Renteria, Miguel E, Budde, Monika, Dipl.-Psych, Weissman, Myrna M, Wray, Naomi R, Bass, Nicholas, Craddock, Nicholas, Smeland, Olav B, Andreassen, Ole A, Mors, Ole, Gejman, Pablo V, Sklar, Pamela, McGrath, Patrick, Hoffmann, Per, McGuffin, Peter, Lee, Phil H, Mortensen, Preben Bo, and Kahn, René S

Subjects
Male, Multifactorial Inheritance, Bipolar Disorder, Polygenic Risk Scoring, Medical and Health Sciences, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Psychiatric Genomics Consortium, Risk Factors, 2.3 Psychological, Genetics, Dipl.-Psych, Humans, 2.1 Biological and endogenous factors, Aetiology, Attempted, Psychiatry, Dr.Med.Sc, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Depressive Disorder, Mood Disorders, Depression, Prevention, Human Genome, Psychology and Cognitive Sciences, Major, Serious Mental Illness, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Brain Disorders, Suicide, Mental Health, Good Health and Well Being, Case-Control Studies, Schizophrenia, Female, M.R.C.Psych, social and economic factors, Genome-Wide Association Study
Abstract

ObjectiveMore than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.MethodsThe samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.ResultsThree genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).ConclusionsThis study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Published
2019

6. Genome-wide association study identifies 30 loci associated with bipolar disorder

Author

Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders

Subjects
Male, Bipolar Disorder, Medical and Health Sciences, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, Aetiology, eQTLGen Consortium, Depressive Disorder, Systems Biology, Human Genome, Major, Single Nucleotide, Biological Sciences, Serious Mental Illness, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Brain Disorders, Mental Health, Psychotic Disorders, Genetic Loci, Case-Control Studies, Schizophrenia, Female, BIOS Consortium, Genome-Wide Association Study, Developmental Biology
Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P

Published
2019

7. Genome-wide association study identifies 30 loci associated with bipolar disorder

Author

Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders

Subjects
Male, Bipolar Disorder, Medical and Health Sciences, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, eQTLGen Consortium, Depressive Disorder, Systems Biology, Human Genome, Major, Single Nucleotide, Biological Sciences, Serious Mental Illness, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Brain Disorders, Mental Health, Psychotic Disorders, Genetic Loci, Case-Control Studies, Schizophrenia, Female, BIOS Consortium, Genome-Wide Association Study, Developmental Biology
Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P

Published
2019

8. Gwas Of Suicide Attempt In Psychiatric Disorders And Association With Major Depression Polygenic Risk Scores

Author

Mullins, Niamh, Bigdeli, Tim B., Børglum, Anders D., Coleman, Jonathan R.I., Demontis, Ditte, Mehta, Divya, Power, Robert A., Ripke, Stephan, Stahl, Eli A., Starnawska, Anna, Anjorin, Adebayo, M.R.C.Psych, Corvin, Aiden, Sanders, Alan R., Forstner, Andreas J., Reif, Andreas, Koller, Anna C., Świątkowska, Beata, Baune, Bernhard T., Müller-Myhsok, Bertram, Penninx, Brenda W.J.H., Pato, Carlos, Zai, Clement, Rujescu, Dan, Hougaard, David M., Quested, Digby, Levinson, Douglas F., Binder, Elisabeth B., Byrne, Enda M., Agerbo, Esben, Dr.Med.Sc, Streit, Fabian, Mayoral, Fermin, Bellivier, Frank, Degenhardt, Franziska, Breen, Gerome, Morken, Gunnar, Turecki, Gustavo, Rouleau, Guy A., Grabe, Hans J., Völzke, Henry, Jones, Ian, Giegling, Ina, Agartz, Ingrid, Melle, Ingrid, Lawrence, Jacob, Walters, James T.R., Strohmaier, Jana, Shi, Jianxin, Hauser, Joanna, Biernacka, Joanna M., Vincent, John B., Kelsoe, John, Strauss, John S., Lissowska, Jolanta, Pimm, Jonathan, Smoller, Jordan W., Guzman-Parra, José, Berger, Klaus, Scott, Laura J., Jones, Lisa A., Azevedo, M. Helena, Trzaskowski, Maciej, Kogevinas, Manolis, Rietschel, Marcella, Boks, Marco, Ising, Marcus, Grigoroiu-Serbanescu, Maria, Hamshere, Marian L., Leboyer, Marion, Frye, Mark, Nöthen, Markus M., Alda, Martin, Preisig, Martin, Nordentoft, Merete, Boehnke, Michael, O’Donovan, Michael C., Owen, Michael J., Pato, Michele T., Renteria, Miguel E., Budde, Monika, Dipl.-Psych, Weissman, Myrna M., Wray, Naomi R., Bass, Nicholas, Craddock, Nicholas, Smeland, Olav B., Andreassen, Ole A., and Mors, Ole

Published
2019
Full Text
View/download PDF

9. Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders

Author

Thygesen, Johan H., Wolfe, Kate, McQuillin, Andrew, Viñas-Jornet, Marina, Baena Díez, Neus, Brison, Nathalie, D'Haenens, Greet, Esteba-Castillo, Susanna, Gabau, Elisabeth, Ribas-Vidal, Núria, Ruiz, Anna, Vermeesch, Joris, Weyts, Eddy, Novell, Ramon, Buggenhout, Griet Van, Strydom, André, Bass, Nicholas, Guitart, Míriam, Vogels, Annick, and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, DNA Copy Number Variations, Comorbidity, 03 medical and health sciences, Neurodevelopmental disorder, Intellectual Disability, Intellectual disability, mental disorders, medicine, Humans, Copy-number variation, Psychiatry, business.industry, Mental Disorders, Middle Aged, medicine.disease, Microarray Analysis, Europe, Psychiatry and Mental health, 030104 developmental biology, Autism spectrum disorder, Schizophrenia, Child Development Disorders, Pervasive, Papers, Female, business
Abstract

BackgroundCopy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.AimsTo determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders.MethodA chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites.ResultsThe yield of pathogenic CNVs was high – 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, PPP < 0.00084) populations.ConclusionsIn the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.Declaration of interestNone.

Published
2018

10. Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

Author

Hosp, Fabian, Vossfeldt, Hannes, Lannfelt, Lars, Holmans, Peter, O'Donovan, Michael, Owen, Michael J., Williams, Julie, Ingelsson, Martin, Lalowski, Maciej, Voigt, Aaron, Selbach, Matthias, Harold, Denise, Abraham, Richard, Hollingworth, Paul, Sims, Rebecca, Gerrish, Amy, Heinig, Matthias, Chapman, Jade, Russo, Giancarlo, Hamshere, Marian, Pahwa, Jaspreet Singh, Escott-Price, Valentina, Dowzell, Kimberley, Williams, Amy, Jones, Nicola, Thomas, Charlene, Stretton, Alexandra, Vasiljevic, Djordje, Morgan, Angharad, Lovestone, Simon, Powell, John, Proitsi, Petroula, Lupton, Michelle K., Brayne, Carol, Rubinsztein, David C., Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Arumughan, Anup, Morgan, Kevin, Brown, Kristelle, Passmore, Peter, Craig, David, McGuinness, Bernadette, Todd, Stephen, Johnston, Janet, Holmes, Clive, Mann, David, Smith, A. David, Wyler, Emanuel, Love, Seth, Kehoe, Patrick G., Hardy, John, Mead, Simon, Fox, Nick, Rossor, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Heun, Reiner, Genetic and Environmental Risk for Alzheimer's Disease GERAD1 Consortium, Schürmann, Britta, Ramirez, Alfredo, Becker, Tim, Herold, Christine, Lacour, André, Drichel, Dmitriy, van den Bussche, Hendrik, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Landthaler, Markus, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Rujescu, Dan, Goate, Alison, Kauwe, John S. K., Cruchaga, Carlos, Nowotny, Petra, Morris, John C., Hubner, Norbert, Mayo, Kevin, Livingston, Gill, Bass, Nicholas J., Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Al-Chalabi, Ammar, Shaw, Christopher E., Singleton, Andrew B., Wanker, Erich E., Guerreiro, Rita, Mühleisen, Thomas W., Nöthen, Markus M., Moebus, Susanne, Jöckel, Karl-Heinz, Klopp, Norman, Wichmann, H-Erich, Carrasquillo, Minerva M., Pankratz, V. Shane, and Younkin, Steven G.

Subjects
Proteomics, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Neurodegenerative Diseases, nervous system diseases, Phenotype, lcsh:Biology (General), Cardiovascular and Metabolic Diseases, Tandem Mass Spectrometry, mental disorders, Animals, Humans, Immunoprecipitation, Function and Dysfunction of the Nervous System, lcsh:QH301-705.5, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Chromatography, Liquid, Genome-Wide Association Study
Abstract

SummarySeveral proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer’s disease (AD), Huntingtin (HTT) for Huntington’s disease, Parkin (PARK2) for Parkinson’s disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.

Published
2015
Full Text
View/download PDF

11. Common polygenic variation enhances risk prediction for Alzheimer's disease

Author

Escott-Price, Valentina, Sims, Rebecca, Passmore, Peter, ODonovan, Michael, Owen, Michael J, Holmes, Clive, Powell, John, Brayne, Carol, Gill, Michael, Mead, Simon, Goate, Alison, Cruchaga, Carlos, Lambert, Jean-Charles, van Duijn, Cornelia, Bannister, Christian, Maier, Wolfgang, Ramirez, Alfredo, Holmans, Peter, Jones, Lesley, Hardy, John, Seshadri, Sudha, Schellenberg, Gerard D, Amouyel, Philippe, Williams, Julie, Abraham, Richard, Harold, Denise, Hollingworth, Paul, Gerrish, Amy, Chapman, Jade, Russo, Giancarlo, Hamshere, Marian, Pahwa, Jaspreet Singh, Dowzell, Kimberley, Williams, Amy, Jones, Nicola, Thomas, Charlene, Vronskaya, Maria, Stretton, Alexandra, Morgan, Angharad, Taylor, Sarah, Lovestone, Simon, Proitsi, Petroula, Lupton, Michelle K, Rubinsztein, David C, Lawlor, Brian, Lynch, Aoibhinn, Brown, Kristelle, Majounie, Elisa, Craig, David, McGuinness, Bernadette, Todd, Stephen, Johnston, Janet, Mann, David, Smith, A David, Love, Seth, Kehoe, Patrick G, Fox, Nick, Rossor, Martin, Badarinarayan, Nandini, Collinge, John, Jessen, Frank, Heun, Reiner, Schürmann, Britta, Becker, Tim, Herold, Christine, Lacour, Andre, Drichel, Dmitriy, van den Bussche, Hendrik, Heuser, Isabella, GERAD/PERADES, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Rujescu, Dan, Kauwe, John S K, Nowotny, Petra, Morris, John C, consortia, IGAP, Mayo, Kevin, Livingston, Gill, Bass, Nicholas J, Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Al-Chalabi, Ammar, Shaw, Christopher E, Singleton, Andrew B, Morgan, Kevin, Guerreiro, Rita, Mühleisen, Thomas W, Nöthen, Markus M., Moebus, Susanne, Jöckel, Karl-Heinz, Klopp, Norman, Wichmann, H-Erich, Carrasquillo, Minerva M, Pankratz, V Shane, Younkin, Steven G, and Epidemiology

Subjects
Apolipoprotein E, Oncology, Risk, Multifactorial Inheritance, medicine.medical_specialty, Genotype, genetics [Alzheimer Disease], Bioinformatics, Logistic regression, Apolipoproteins E, Alzheimer Disease, Positive predicative value, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic Testing, genetics [Genetic Predisposition to Disease], genetics [Multifactorial Inheritance], Alleles, Receiver operating characteristic, Case-control study, Genetic Variation, Original Articles, medicine.disease, Confidence interval, genetics [Genetic Variation], Logistic Models, ROC Curve, Case-Control Studies, genetics [Apolipoproteins E], Neurology (clinical), Alzheimer's disease, Psychology, Genome-Wide Association Study
Abstract

The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample. The disease prediction accuracy was investigated in a subset of the IGAP data, a sample of 3049 cases and 1554 controls (for whom APOE genotype data were available) by means of sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and positive and negative predictive values. We observed significant evidence for a polygenic component enriched in Alzheimer's disease (P = 4.9 × 10(-26)). This enrichment remained significant after APOE and other genome-wide associated regions were excluded (P = 3.4 × 10(-19)). The best prediction accuracy AUC = 78.2% (95% confidence interval 77-80%) was achieved by a logistic regression model with APOE, the polygenic score, sex and age as predictors. In conclusion, Alzheimer's disease has a significant polygenic component, which has predictive utility for Alzheimer's disease risk and could be a valuable research tool complementing experimental designs, including preventative clinical trials, stem cell selection and high/low risk clinical studies. In modelling a range of sample disease prevalences, we found that polygenic scores almost doubles case prediction from chance with increased prediction at polygenic extremes.

Published
2015

12. Does rare matter? Copy number variants at 16p11.2 and the risk of psychosis: A systematic review of literature and meta-analysis

Author

Giaroli, Giovanni, Bass, Nicholas, Strydom, Andre, Rantell, Khadijia, and McQuillin, Andrew

Subjects
Psychiatry and Mental health, Schizoaffective disorder, Copy number variation, Duplication, CNV, Schizophrenia, Bipolar disorders, 16p11.2, Psychosis, Biological Psychiatry
Abstract

BackgroundIn the last 5years an increasing number of studies have found that individuals who have micro-duplications at 16p11.2 may have an increased risk of mental disorders including psychotic syndromes.ObjectiveOur main aim was to review all the evidence in the literature for the association between copy number variants (CNVs) at 16p11.2 and psychosis.MethodsWe have conducted a systematic review and a meta-analysis utilising the PRISMA statement criteria. We included all original studies (published in English) which presented data on CNVs at 16p11.2 in patients affected by schizophrenia, schizoaffective disorder or bipolar disorder.ResultsWe retrieved 15 articles which fulfilled our inclusion criteria. Eleven articles were subsequently selected for a meta-analysis that showed a 10 fold increased risk of psychosis in patients with proximal 16p11.2 duplications. We conducted a second meta-analysis of those studies with low risk of overlap in order to obtain the largest possible sample with the lowest risk of repeated results: 5 studies were selected and we found an odds ratio (OR) of 14.4 (CI=5.2–39.8; p

Published
2014
Full Text
View/download PDF

13. New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis

Author

Lee, S Hong, Byrne, Enda M, Hultman, Christina M, Kähler, Anna, Vinkhuyzen, Anna AE, Ripke, Stephan, Andreassen, Ole A, Frisell, Thomas, Gusev, Alexander, Hu, Xinli, Karlsson, Robert, Mantzioris, Vasilis X, McGrath, John J, Mehta, Divya, Stahl, Eli A, Zhao, Qiongyi, Kendler, Kenneth S, Sullivan, Patrick F, Price, Alkes L, O'Donovan, Michael, Okada, Yukinori, Mowry, Bryan J, Raychaudhuri, Soumya, Wray, Naomi R, Schizophrenia Working Group of the Psychiatric Genomics Consortium and Rheumatoid Arthritis Consortium International, Schizophrenia Working Group of the Psychiatric Genomics Consortium Authors, Byerley, William, Cahn, Wiepke, Cantor, Rita M, Cichon, Sven, Cormican, Paul, Curtis, David, Djurovic, Srdjan, Escott-Price, Valentina, Gejman, Pablo V, Georgieva, Lyudmila, Giegling, Ina, Hansen, Thomas F, Ingason, Andrés, Kim, Yunjung, Konte, Bettina, Lee, Phil H, McIntosh, Andrew, McQuillin, Andrew, Morris, Derek W, Nöthen, Markus M, O'Dushlaine, Colm, Olincy, Ann, Olsen, Line, Pato, Carlos N, Pato, Michele T, Pickard, Benjamin S, Posthuma, Danielle, Rasmussen, Henrik B, Rietschel, Marcella, Rujescu, Dan, Schulze, Thomas G, Silverman, Jeremy M, Thirumalai, Srinivasa, Werge, Thomas, Schizophrenia Working Group of the Psychiatric Genomics Consortium Collaborators, Agartz, Ingrid, Amin, Farooq, Azevedo, Maria H, Bass, Nicholas, Black, Donald W, Blackwood, Douglas HR, Bruggeman, Richard, Buccola, Nancy G, Choudhury, Khalid, Cloninger, Robert C, Corvin, Aiden, Craddock, Nicholas, Daly, Mark J, Datta, Susmita, Donohoe, Gary J, Duan, Jubao, Dudbridge, Frank, Fanous, Ayman, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Gill, Michael, Gurling, Hugh, De Haan, Lieuwe, Hamshere, Marian L, Hartmann, Annette M, Holmans, Peter A, Kahn, René S, Keller, Matthew C, Kenny, Elaine, Kirov, George K, Krabbendam, Lydia, Krasucki, Robert, Lawrence, Jacob, Lencz, Todd, Levinson, Douglas F, Lieberman, Jeffrey A, and Lin, Dan-Yu

Subjects
Adult, Male, Rheumatoid Arthritis Consortium International Collaborators, Adolescent, Epidemiology, Autoimmune Disease, Cohort Studies, Young Adult, Clinical Research, Rheumatoid, Genetics, Schizophrenia Working Group of the Psychiatric Genomics Consortium Authors, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, Aetiology, Arthritis, Inflammatory and immune system, Human Genome, Statistics, Genetic Variation, Single Nucleotide, Middle Aged, Schizophrenia Working Group of the Psychiatric Genomics Consortium Collaborators, Serious Mental Illness, Brain Disorders, Rheumatoid Arthritis Consortium International Authors, Cross-Sectional Studies, Mental Health, Schizophrenia Working Group of the Psychiatric Genomics Consortium and Rheumatoid Arthritis Consortium International, Schizophrenia, Public Health and Health Services, Female, Gene-Environment Interaction, Genome-Wide Association Study
Abstract

BackgroundA long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders.MethodsWe use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born.ResultsWe estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090).ConclusionsOur results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context.

Published
2015

14. Joint Analysis Of Psychiatric Disorders Increases Accuracy Of Risk Prediction For Schizophrenia, Bipolar Disorder, And Major Depressive Disorder

Author

Maier, Robert, Moser, Gerhard, Chen, Guo-Bo, Ripke, Stephan, Coryell, William, Potash, James B., Scheftner, William A., Shi, Jianxin, Weissman, Myrna M., Hultman, Christina M., Landén, Mikael, Levinson, Douglas F., Kendler, Kenneth S., Smoller, Jordan W., Wray, Naomi R., Lee, S. Hong, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A., Anjorin, Adebayo, Anney, Richard, Arking, Dan E., Asherson, Philip, Azevedo, Maria H., Backlund, Lena, Badner, Judith A., Bailey, Anthony J., Banaschewski, Tobias, Barchas, Jack D., Barnes, Michael R., Barrett, Thomas B., Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah E., Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B., Black, Donald W., Blackwood, Douglas H.R., Bloss, Cinnamon S., Boehnke, Michael, Boomsma, Dorret I., Breen, Gerome, Breuer, René, Bruggeman, Richard, Buccola, Nancy G., Buitelaar, Jan K., Bunney, William E., Buxbaum, Joseph D., Byerley, William F., Caesar, Sian, Cahn, Wiepke, Cantor, Rita M., Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C. Robert, Collier, David A., Cook, Edwin H., Coon, Hilary, Cormand, Bru, Cormican, Paul, Corvin, Aiden, Coryell, William H., Craddock, Nicholas, Craig, David W., Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L., Curtis, David, Czamara, Darina, Daly, Mark J., Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J., Degenhardt, Franziska, Devlin, Bernie, Djurovic, Srdjan, Donohoe, Gary J., Doyle, Alysa E., Duan, Jubao, and Dudbridge, Frank

Published
2015
Full Text
View/download PDF

15. Linking Protective GAB2 Variants, Increased Cortical GAB2 Expression and Decreased Alzheimer's Disease Pathology

Author

Zou, Fanggeng, Belbin, Olivia, Petersen, Ronald C, disease, Genetic and Environmental Risk for Alzheimer’s, Morgan, Kevin, Younkin, Steven G, Harold, Denise, Sims, Rebecca, Gerrish, Amy, Chapman, Jade, Moskvina, Valentina, Abraham, Richard, Carrasquillo, Minerva M, Hollingworth, Paul, Hamshere, Marian, Pahwa, Jaspreet Singh, Dowzell, Kimberley, Williams, Amy, Jones, Nicola, Thomas, Charlene, Stretton, Alexandra, Morgan, Angharad, Williams, Kate, Culley, Oliver J, Lovestone, Simon, Powell, John, Proitsi, Petroula, Lupton, Michelle K, Brayne, Carol, Rubinsztein, David C, Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Hunter, Talisha A, Brown, Kristelle, Passmore, Peter, Craig, David, McGuinness, Bernadette, Johnston, Janet A, Todd, Stephen, Holmes, Clive, Mann, David, Smith, A David, Love, Seth, Ma, Li, Kehoe, Patrick G, Hardy, John, Guerreiro, Rita, Singleton, Andrew, Mead, Simon, Fox, Nick, Rossor, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Bisceglio, Gina D, Heun, Reiner, Schürmann, Britta, Ramirez, Alfredo, Herold, Christine, Lacour, André, Drichel, Dmitriy, van den Bussche, Hendrik, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Allen, Mariet, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Rujescu, Dan, Goate, Alison, Kauwe, John S K, Cruchaga, Carlos, Nowotny, Petra, Morris, John C, Dickson, Dennis W, Mayo, Kevin, Livingston, Gill, Bass, Nicholas J, Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Nöthen, Markus M, Holmans, Peter, O'Donovan, Michael, Graff-Radford, Neill R, Owen, Michael J, Williams, Julie, and Wiltfang, Jens (Beitragende*r)

Subjects
Male, Pathology, Heredity, Medizin, lcsh:Medicine, Gene Expression, genetics [Alzheimer Disease], pathology [Alzheimer Disease], 0302 clinical medicine, Polymorphism (computer science), Risk Factors, genetics [Adaptor Proteins, Signal Transducing], Senile plaques, lcsh:Science, 0303 health sciences, Multidisciplinary, Temporal Lobe, Neurology, genetics [Polymorphism, Single Nucleotide], Medicine, Female, Alzheimer's disease, Research Article, medicine.medical_specialty, Genotypes, genetics [Genetic Loci], Biology, metabolism [RNA, Messenger], Polymorphism, Single Nucleotide, metabolism [Temporal Lobe], Cell Line, Molecular Genetics, 03 medical and health sciences, metabolism [Adaptor Proteins, Signal Transducing], genetics [RNA, Messenger], Genetic Heterogeneity, Apolipoproteins E, Meta-Analysis as Topic, Alzheimer Disease, genetics [Haplotypes], medicine, GAB2 protein, human, Genetics, Humans, Genetic Predisposition to Disease, ddc:610, RNA, Messenger, Allele, Genetic Association Studies, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Aged, Evolutionary Biology, Population Biology, Genetic heterogeneity, lcsh:R, Case-control study, Computational Biology, Neurofibrillary tangle, pathology [Temporal Lobe], Human Genetics, Epistasis, Genetic, Odds ratio, medicine.disease, R1, Haplotypes, Genetic Loci, Case-Control Studies, Postmortem Changes, Genetics of Disease, North America, Genetic Polymorphism, Epistasis, genetics [Apolipoproteins E], lcsh:Q, Dementia, 030217 neurology & neurosurgery, Population Genetics
Abstract

GRB-associated binding protein 2 (GAB2) represents a compelling genome-wide association signal for late-onset Alzheimer's disease (LOAD) with reported odds ratios (ORs) ranging from 0.75-0.85. We tested eight GAB2 variants in four North American Caucasian case-control series (2,316 LOAD, 2,538 controls) for association with LOAD. Meta-analyses revealed ORs ranging from (0.61-1.20) with no significant association (all p>0.32). Four variants were hetergeneous across the populations (all p

Published
2013

Catalog

Books, media, physical & digital resources
See catalog results