Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway.
Kristin K. Nicodemus,Kristin K. Nicodemus,April Hargreaves,Derek W. Morris,Richard Anney,Michael Gill,Aiden Corvin,Gary Donohoe,Gary Donohoe +8 more
TL;DR: A role for the ZNF804A pathway in IQ, memory, and social cognition in cases is supported, and it is shown that epistasis increases the variation explained above the contribution of the polygenic score.
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Abstract: DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis).
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Genetic insights into the neurodevelopmental origins of schizophrenia.
TL;DR: The neurodevelopmental model of schizophrenia is revisits from a current genetics perspective, delineating the complex genetic basis of the disorder and highlighting gene expression and epigenetic analyses of post-mortem cortical tissue that suggest that early brain development mediates genetic risk associated with schizophrenia.
458
Polygenic associations of neurodevelopmental genes in suicide attempt
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Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland ( n =19 762), UK Biobank ( n =24 048) and the English Longitudinal Study of Ageing ( n =5766)
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TL;DR: In this article, the authors used the most recent published data from Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium's genome-wide association study of regional brain volume to test whether there is shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and major depressive disorder (MDD).
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TL;DR: The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade as discussed by the authors, and a review summarizes the pathogenesis of schizophrenia, especially negative symptoms, from the perspectives of genetics and epigenetics.
Closing the translational gap between mutant mouse models and the clinical reality of psychotic illness.
TL;DR: This review will consider recent advances in the field whereby mutant mouse models seek to reflect increasing knowledge of psychotic illness, focusing on four main themes.
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Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
Shaun Purcell,Shaun Purcell,Naomi R. Wray,Jennifer Stone,Jennifer Stone,Peter M. Visscher,Michael Conlon O'Donovan,Patrick F. Sullivan,Pamela Sklar,Pamela Sklar,Douglas M. Ruderfer,Andrew McQuillin,Derek W. Morris,Colm O'Dushlaine,Aiden Corvin,Peter Holmans,Stuart MacGregor,Hugh Gurling,Douglas Blackwood,Nicholas John Craddock,Michael Gill,Christina M. Hultman,Christina M. Hultman,George Kirov,Paul Lichtenstein,Walter J. Muir,Michael John Owen,Carlos N. Pato,Edward M. Scolnick,Edward M. Scolnick,David St Clair,Nigel Williams,Lyudmila Georgieva,Ivan Nikolov,Nadine Norton,Hywel Williams,Draga Toncheva,Vihra Milanova,Emma Flordal Thelander,Patrick Sullivan,Elaine Kenny,Emma M. Quinn,Khalid Choudhury,Susmita Datta,Jonathan Pimm,Srinivasa Thirumalai,Vinay Puri,Robert Krasucki,Jacob Lawrence,Digby Quested,Nicholas Bass,Caroline Crombie,Gillian Fraser,Soh Leh Kuan,Nicholas Walker,Kevin A. McGhee,Ben S. Pickard,P. Malloy,Alan W Maclean,Margaret Van Beck,Michele T. Pato,Helena Medeiros,Frank A. Middleton,Célia Barreto Carvalho,Christopher P. Morley,Ayman H. Fanous,David V. Conti,James A. Knowles,Carlos Ferreira,António Macedo,M. Helena Azevedo,Andrew Kirby,Andrew Kirby,Manuel A. R. Ferreira,Manuel A. R. Ferreira,Mark J. Daly,Mark J. Daly,Kimberly Chambert,Finny G Kuruvilla,Stacey Gabriel,Kristin G. Ardlie,Jennifer L. Moran +81 more
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Genome-wide association study identifies five new schizophrenia loci
Stephan Ripke,Alan R. Sanders,Kenneth S. Kendler,Douglas F. Levinson,Pamela Sklar,Pamela Sklar,Peter Holmans,Danyu Lin,Jubao Duan,Roel A. Ophoff,Roel A. Ophoff,Ole A. Andreassen,Edward M. Scolnick,Sven Cichon,David St Clair,Aiden Corvin,Hugh Gurling,Thomas Werge,Dan Rujescu,Douglas Blackwood,Carlos N. Pato,Anil K. Malhotra,Anil K. Malhotra,Shaun Purcell,Frank Dudbridge,Benjamin M. Neale,Lizzy Rossin,Peter M. Visscher,Danielle Posthuma,Douglas M. Ruderfer,Ayman H. Fanous,Ayman H. Fanous,Ayman H. Fanous,Hreinn Stefansson,Stacy Steinberg,Bryan J. Mowry,Vera Golimbet,Marc De Hert,Erik G. Jönsson,István Bitter,Olli Pietiläinen,David A. Collier,Sarah Tosato,Ingrid Agartz,Margot Albus,Madeline Alexander,Richard Amdur,Richard Amdur,Farooq Amin,Farooq Amin,Nicholas Bass,Sarah E. Bergen,Donald W. Black,Anders D. Børglum,Matthew A. Brown,Richard Bruggeman,Nancy G. Buccola,William Byerley,Wiepke Cahn,Rita M. Cantor,Vaughan J. Carr,Stanley V. Catts,Khalid Choudhury,C. Robert Cloninger,Paul Cormican,Nicholas John Craddock,Patrick Danoy,Susmita Datta,Lieuwe de Haan,Ditte Demontis,Dimitris Dikeos,Srdjan Djurovic,Peter Donnelly,Gary Donohoe,L. Duong,Sarah Dwyer,Anders Fink-Jensen,Robert Freedman,Nelson B. Freimer,Marion Friedl,Lyudmila Georgieva,Ina Giegling,Michael Gill,Birte Glenthøj,Stephanie Godard,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Annette M. Hartmann,Frans Henskens,David M. Hougaard,Christina M. Hultman,Andres Ingason,Assen Jablensky,Klaus D. Jakobsen,M. Jay,Gesche Jürgens,René S. Kahn,Matthew C. Keller,Gunter Kenis,Elaine Kenny,Yunjung Kim,George Kirov,H. Konnerth,Bettina Konte,Lydia Krabbendam,Robert Krasucki,Virginia K. Lasseter,Claudine Laurent,Jacob Lawrence,Todd Lencz,Todd Lencz,F. Bernard Lerer,Kung Yee Liang,Paul Lichtenstein,Jeffrey A. Lieberman,Don H. Linszen,Jouko Lönnqvist,Carmel M. Loughland,Alan W Maclean,Brion S. Maher,Wolfgang Maier,J. Mallet,P. Malloy,Manuel Mattheisen,Morten Mattingsdal,Kevin A. McGhee,John J. McGrath,Andrew M. McIntosh,Duncan E. McLean,Andrew McQuillin,Ingrid Melle,Patricia T. Michie,Vihra Milanova,Derek W. Morris,Ole Mors,Preben Bo Mortensen,Valentina Moskvina,Pierandrea Muglia,Inez Myin-Germeys,Deborah A. Nertney,Gerald Nestadt,Jimmi Nielsen,Ivan Nikolov,Merete Nordentoft,Nadine Norton,Markus M. Nöthen,Colm O'Dushlaine,Ann Olincy,Line Olsen,F. Anthony O'Neill,Torben F. Ørntoft,Michael John Owen,Christos Pantelis,George N. Papadimitriou,Michele T. Pato,Leena Peltonen,Leena Peltonen,Hannes Petursson,Ben S. Pickard,Jonathan Pimm,Ann E. Pulver,Vinay Puri,Digby Quested,Emma M. Quinn,Henrik B. Rasmussen,János Réthelyi,R. Ribble,Marcella Rietschel,Marcella Rietschel,Brien P. Riley,Mirella Ruggeri,Ulrich Schall,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Sibylle G. Schwab,Rodney J. Scott,Jianxin Shi,Engilbert Sigurdsson,Jeremy M. Silverman,Jeremy M. Silverman,Chris C. A. Spencer,Kari Stefansson,Amy Strange,Eric Strengman,T. Scott Stroup,Jaana Suvisaari,Lars Terenius,Srinivasa Thirumalai,Johan H. Thygesen,Sally Timm,Draga Toncheva,Edwin J. C. G. van den Oord,Jim van Os,Ruud van Winkel,Ruud van Winkel,Jan H. Veldink,Dermot Walsh,August G. Wang,Durk Wiersma,Dieter B. Wildenauer,Hywel Williams,Nigel Williams,Brandon Wormley,Stan Zammit,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan,Mark J. Daly,Pablo V. Gejman +210 more
TL;DR: The authors examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects.
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