Literature DB >> 27786187

Translating genome-wide association findings into new therapeutics for psychiatry.

Gerome Breen1,2, Qingqin Li3, Bryan L Roth4,5,6, Patricio O'Donnell7, Michael Didriksen8, Ricardo Dolmetsch9, Paul F O'Reilly1, Héléna A Gaspar1,2, Husseini Manji3, Christopher Huebel1,2, John R Kelsoe10, Dheeraj Malhotra11, Alessandro Bertolino12, Danielle Posthuma13,14, Pamela Sklar15,16,17, Shitij Kapur18, Patrick F Sullivan19,20, David A Collier1,2,21, Howard J Edenberg22,23.   

Abstract

Genome-wide association studies (GWAS) in psychiatry, once they reach sufficient sample size and power, have been enormously successful. The Psychiatric Genomics Consortium (PGC) aims for mega-analyses with sample sizes that will grow to >1 million individuals in the next 5 years. This should lead to hundreds of new findings for common genetic variants across nine psychiatric disorders studied by the PGC. The new targets discovered by GWAS have the potential to restart largely stalled psychiatric drug development pipelines, and the translation of GWAS findings into the clinic is a key aim of the recently funded phase 3 of the PGC. This is not without considerable technical challenges. These approaches complement the other main aim of GWAS studies, risk prediction approaches for improving detection, differential diagnosis, and clinical trial design. This paper outlines the motivations, technical and analytical issues, and the plans for translating PGC phase 3 findings into new therapeutics.

Entities:  

Mesh:

Year:  2016        PMID: 27786187      PMCID: PMC5676453          DOI: 10.1038/nn.4411

Source DB:  PubMed          Journal:  Nat Neurosci        ISSN: 1097-6256            Impact factor:   24.884


  43 in total

1.  Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis.

Authors:  Esben Agerbo; Patrick F Sullivan; Bjarni J Vilhjálmsson; Carsten B Pedersen; Ole Mors; Anders D Børglum; David M Hougaard; Mads V Hollegaard; Sandra Meier; Manuel Mattheisen; Stephan Ripke; Naomi R Wray; Preben B Mortensen
Journal:  JAMA Psychiatry       Date:  2015-07       Impact factor: 21.596

2.  Prediction of individual genetic risk to disease from genome-wide association studies.

Authors:  Naomi R Wray; Michael E Goddard; Peter M Visscher
Journal:  Genome Res       Date:  2007-09-04       Impact factor: 9.043

3.  Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

Authors:  Simone de Jong; Lewis R Vidler; Younes Mokrab; David A Collier; Gerome Breen
Journal:  J Psychopharmacol       Date:  2016-06-14       Impact factor: 4.153

4.  Integrative approaches for large-scale transcriptome-wide association studies.

Authors:  Alexander Gusev; Arthur Ko; Huwenbo Shi; Gaurav Bhatia; Wonil Chung; Brenda W J H Penninx; Rick Jansen; Eco J C de Geus; Dorret I Boomsma; Fred A Wright; Patrick F Sullivan; Elina Nikkola; Marcus Alvarez; Mete Civelek; Aldons J Lusis; Terho Lehtimäki; Emma Raitoharju; Mika Kähönen; Ilkka Seppälä; Olli T Raitakari; Johanna Kuusisto; Markku Laakso; Alkes L Price; Päivi Pajukanta; Bogdan Pasaniuc
Journal:  Nat Genet       Date:  2016-02-08       Impact factor: 38.330

5.  Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial.

Authors:  Kevin Fitzgerald; Maria Frank-Kamenetsky; Svetlana Shulga-Morskaya; Abigail Liebow; Brian R Bettencourt; Jessica E Sutherland; Renta M Hutabarat; Valerie A Clausen; Verena Karsten; Jeffrey Cehelsky; Saraswathy V Nochur; Victor Kotelianski; Jay Horton; Timothy Mant; Joseph Chiesa; James Ritter; Malathy Munisamy; Akshay K Vaishnaw; Jared A Gollob; Amy Simon
Journal:  Lancet       Date:  2013-10-03       Impact factor: 79.321

6.  Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

Authors:  Nick Craddock; Matthew E Hurles; Niall Cardin; Richard D Pearson; Vincent Plagnol; Samuel Robson; Damjan Vukcevic; Chris Barnes; Donald F Conrad; Eleni Giannoulatou; Chris Holmes; Jonathan L Marchini; Kathy Stirrups; Martin D Tobin; Louise V Wain; Chris Yau; Jan Aerts; Tariq Ahmad; T Daniel Andrews; Hazel Arbury; Anthony Attwood; Adam Auton; Stephen G Ball; Anthony J Balmforth; Jeffrey C Barrett; Inês Barroso; Anne Barton; Amanda J Bennett; Sanjeev Bhaskar; Katarzyna Blaszczyk; John Bowes; Oliver J Brand; Peter S Braund; Francesca Bredin; Gerome Breen; Morris J Brown; Ian N Bruce; Jaswinder Bull; Oliver S Burren; John Burton; Jake Byrnes; Sian Caesar; Chris M Clee; Alison J Coffey; John M C Connell; Jason D Cooper; Anna F Dominiczak; Kate Downes; Hazel E Drummond; Darshna Dudakia; Andrew Dunham; Bernadette Ebbs; Diana Eccles; Sarah Edkins; Cathryn Edwards; Anna Elliot; Paul Emery; David M Evans; Gareth Evans; Steve Eyre; Anne Farmer; I Nicol Ferrier; Lars Feuk; Tomas Fitzgerald; Edward Flynn; Alistair Forbes; Liz Forty; Jayne A Franklyn; Rachel M Freathy; Polly Gibbs; Paul Gilbert; Omer Gokumen; Katherine Gordon-Smith; Emma Gray; Elaine Green; Chris J Groves; Detelina Grozeva; Rhian Gwilliam; Anita Hall; Naomi Hammond; Matt Hardy; Pile Harrison; Neelam Hassanali; Husam Hebaishi; Sarah Hines; Anne Hinks; Graham A Hitman; Lynne Hocking; Eleanor Howard; Philip Howard; Joanna M M Howson; Debbie Hughes; Sarah Hunt; John D Isaacs; Mahim Jain; Derek P Jewell; Toby Johnson; Jennifer D Jolley; Ian R Jones; Lisa A Jones; George Kirov; Cordelia F Langford; Hana Lango-Allen; G Mark Lathrop; James Lee; Kate L Lee; Charlie Lees; Kevin Lewis; Cecilia M Lindgren; Meeta Maisuria-Armer; Julian Maller; John Mansfield; Paul Martin; Dunecan C O Massey; Wendy L McArdle; Peter McGuffin; Kirsten E McLay; Alex Mentzer; Michael L Mimmack; Ann E Morgan; Andrew P Morris; Craig Mowat; Simon Myers; William Newman; Elaine R Nimmo; Michael C O'Donovan; Abiodun Onipinla; Ifejinelo Onyiah; Nigel R Ovington; Michael J Owen; Kimmo Palin; Kirstie Parnell; David Pernet; John R B Perry; Anne Phillips; Dalila Pinto; Natalie J Prescott; Inga Prokopenko; Michael A Quail; Suzanne Rafelt; Nigel W Rayner; Richard Redon; David M Reid; Susan M Ring; Neil Robertson; Ellie Russell; David St Clair; Jennifer G Sambrook; Jeremy D Sanderson; Helen Schuilenburg; Carol E Scott; Richard Scott; Sheila Seal; Sue Shaw-Hawkins; Beverley M Shields; Matthew J Simmonds; Debbie J Smyth; Elilan Somaskantharajah; Katarina Spanova; Sophia Steer; Jonathan Stephens; Helen E Stevens; Millicent A Stone; Zhan Su; Deborah P M Symmons; John R Thompson; Wendy Thomson; Mary E Travers; Clare Turnbull; Armand Valsesia; Mark Walker; Neil M Walker; Chris Wallace; Margaret Warren-Perry; Nicholas A Watkins; John Webster; Michael N Weedon; Anthony G Wilson; Matthew Woodburn; B Paul Wordsworth; Allan H Young; Eleftheria Zeggini; Nigel P Carter; Timothy M Frayling; Charles Lee; Gil McVean; Patricia B Munroe; Aarno Palotie; Stephen J Sawcer; Stephen W Scherer; David P Strachan; Chris Tyler-Smith; Matthew A Brown; Paul R Burton; Mark J Caulfield; Alastair Compston; Martin Farrall; Stephen C L Gough; Alistair S Hall; Andrew T Hattersley; Adrian V S Hill; Christopher G Mathew; Marcus Pembrey; Jack Satsangi; Michael R Stratton; Jane Worthington; Panos Deloukas; Audrey Duncanson; Dominic P Kwiatkowski; Mark I McCarthy; Willem Ouwehand; Miles Parkes; Nazneen Rahman; John A Todd; Nilesh J Samani; Peter Donnelly
Journal:  Nature       Date:  2010-04-01       Impact factor: 49.962

Review 7.  Developing and evaluating polygenic risk prediction models for stratified disease prevention.

Authors:  Nilanjan Chatterjee; Jianxin Shi; Montserrat García-Closas
Journal:  Nat Rev Genet       Date:  2016-05-03       Impact factor: 53.242

8.  A polygenic burden of rare disruptive mutations in schizophrenia.

Authors:  Shaun M Purcell; Jennifer L Moran; Menachem Fromer; Douglas Ruderfer; Nadia Solovieff; Panos Roussos; Colm O'Dushlaine; Kimberly Chambert; Sarah E Bergen; Anna Kähler; Laramie Duncan; Eli Stahl; Giulio Genovese; Esperanza Fernández; Mark O Collins; Noboru H Komiyama; Jyoti S Choudhary; Patrik K E Magnusson; Eric Banks; Khalid Shakir; Kiran Garimella; Tim Fennell; Mark DePristo; Seth G N Grant; Stephen J Haggarty; Stacey Gabriel; Edward M Scolnick; Eric S Lander; Christina M Hultman; Patrick F Sullivan; Steven A McCarroll; Pamela Sklar
Journal:  Nature       Date:  2014-01-22       Impact factor: 49.962

9.  Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Authors:  S Hong Lee; Stephan Ripke; Benjamin M Neale; Stephen V Faraone; Shaun M Purcell; Roy H Perlis; Bryan J Mowry; Anita Thapar; Michael E Goddard; John S Witte; Devin Absher; Ingrid Agartz; Huda Akil; Farooq Amin; Ole A Andreassen; Adebayo Anjorin; Richard Anney; Verneri Anttila; Dan E Arking; Philip Asherson; Maria H Azevedo; Lena Backlund; Judith A Badner; Anthony J Bailey; Tobias Banaschewski; Jack D Barchas; Michael R Barnes; Thomas B Barrett; Nicholas Bass; Agatino Battaglia; Michael Bauer; Mònica Bayés; Frank Bellivier; Sarah E Bergen; Wade Berrettini; Catalina Betancur; Thomas Bettecken; Joseph Biederman; Elisabeth B Binder; Donald W Black; Douglas H R Blackwood; Cinnamon S Bloss; Michael Boehnke; Dorret I Boomsma; Gerome Breen; René Breuer; Richard Bruggeman; Paul Cormican; Nancy G Buccola; Jan K Buitelaar; William E Bunney; Joseph D Buxbaum; William F Byerley; Enda M Byrne; Sian Caesar; Wiepke Cahn; Rita M Cantor; Miguel Casas; Aravinda Chakravarti; Kimberly Chambert; Khalid Choudhury; Sven Cichon; C Robert Cloninger; David A Collier; Edwin H Cook; Hilary Coon; Bru Cormand; Aiden Corvin; William H Coryell; David W Craig; Ian W Craig; Jennifer Crosbie; Michael L Cuccaro; David Curtis; Darina Czamara; Susmita Datta; Geraldine Dawson; Richard Day; Eco J De Geus; Franziska Degenhardt; Srdjan Djurovic; Gary J Donohoe; Alysa E Doyle; Jubao Duan; Frank Dudbridge; Eftichia Duketis; Richard P Ebstein; Howard J Edenberg; Josephine Elia; Sean Ennis; Bruno Etain; Ayman Fanous; Anne E Farmer; I Nicol Ferrier; Matthew Flickinger; Eric Fombonne; Tatiana Foroud; Josef Frank; Barbara Franke; Christine Fraser; Robert Freedman; Nelson B Freimer; Christine M Freitag; Marion Friedl; Louise Frisén; Louise Gallagher; Pablo V Gejman; Lyudmila Georgieva; Elliot S Gershon; Daniel H Geschwind; Ina Giegling; Michael Gill; Scott D Gordon; Katherine Gordon-Smith; Elaine K Green; Tiffany A Greenwood; Dorothy E Grice; Magdalena Gross; Detelina Grozeva; Weihua Guan; Hugh Gurling; Lieuwe De Haan; Jonathan L Haines; Hakon Hakonarson; Joachim Hallmayer; Steven P Hamilton; Marian L Hamshere; Thomas F Hansen; Annette M Hartmann; Martin Hautzinger; Andrew C Heath; Anjali K Henders; Stefan Herms; Ian B Hickie; Maria Hipolito; Susanne Hoefels; Peter A Holmans; Florian Holsboer; Witte J Hoogendijk; Jouke-Jan Hottenga; Christina M Hultman; Vanessa Hus; Andrés Ingason; Marcus Ising; Stéphane Jamain; Edward G Jones; Ian Jones; Lisa Jones; Jung-Ying Tzeng; Anna K Kähler; René S Kahn; Radhika Kandaswamy; Matthew C Keller; James L Kennedy; Elaine Kenny; Lindsey Kent; Yunjung Kim; George K Kirov; Sabine M Klauck; Lambertus Klei; James A Knowles; Martin A Kohli; Daniel L Koller; Bettina Konte; Ania Korszun; Lydia Krabbendam; Robert Krasucki; Jonna Kuntsi; Phoenix Kwan; Mikael Landén; Niklas Långström; Mark Lathrop; Jacob Lawrence; William B Lawson; Marion Leboyer; David H Ledbetter; Phil H Lee; Todd Lencz; Klaus-Peter Lesch; Douglas F Levinson; Cathryn M Lewis; Jun Li; Paul Lichtenstein; Jeffrey A Lieberman; Dan-Yu Lin; Don H Linszen; Chunyu Liu; Falk W Lohoff; Sandra K Loo; Catherine Lord; Jennifer K Lowe; Susanne Lucae; Donald J MacIntyre; Pamela A F Madden; Elena Maestrini; Patrik K E Magnusson; Pamela B Mahon; Wolfgang Maier; Anil K Malhotra; Shrikant M Mane; Christa L Martin; Nicholas G Martin; Manuel Mattheisen; Keith Matthews; Morten Mattingsdal; Steven A McCarroll; Kevin A McGhee; James J McGough; Patrick J McGrath; Peter McGuffin; Melvin G McInnis; Andrew McIntosh; Rebecca McKinney; Alan W McLean; Francis J McMahon; William M McMahon; Andrew McQuillin; Helena Medeiros; Sarah E Medland; Sandra Meier; Ingrid Melle; Fan Meng; Jobst Meyer; Christel M Middeldorp; Lefkos Middleton; Vihra Milanova; Ana Miranda; Anthony P Monaco; Grant W Montgomery; Jennifer L Moran; Daniel Moreno-De-Luca; Gunnar Morken; Derek W Morris; Eric M Morrow; Valentina Moskvina; Pierandrea Muglia; Thomas W Mühleisen; Walter J Muir; Bertram Müller-Myhsok; Michael Murtha; Richard M Myers; Inez Myin-Germeys; Michael C Neale; Stan F Nelson; Caroline M Nievergelt; Ivan Nikolov; Vishwajit Nimgaonkar; Willem A Nolen; Markus M Nöthen; John I Nurnberger; Evaristus A Nwulia; Dale R Nyholt; Colm O'Dushlaine; Robert D Oades; Ann Olincy; Guiomar Oliveira; Line Olsen; Roel A Ophoff; Urban Osby; Michael J Owen; Aarno Palotie; Jeremy R Parr; Andrew D Paterson; Carlos N Pato; Michele T Pato; Brenda W Penninx; Michele L Pergadia; Margaret A Pericak-Vance; Benjamin S Pickard; Jonathan Pimm; Joseph Piven; Danielle Posthuma; James B Potash; Fritz Poustka; Peter Propping; Vinay Puri; Digby J Quested; Emma M Quinn; Josep Antoni Ramos-Quiroga; Henrik B Rasmussen; Soumya Raychaudhuri; Karola Rehnström; Andreas Reif; Marta Ribasés; John P Rice; Marcella Rietschel; Kathryn Roeder; Herbert Roeyers; Lizzy Rossin; Aribert Rothenberger; Guy Rouleau; Douglas Ruderfer; Dan Rujescu; Alan R Sanders; Stephan J Sanders; Susan L Santangelo; Joseph A Sergeant; Russell Schachar; Martin Schalling; Alan F Schatzberg; William A Scheftner; Gerard D Schellenberg; Stephen W Scherer; Nicholas J Schork; Thomas G Schulze; Johannes Schumacher; Markus Schwarz; Edward Scolnick; Laura J Scott; Jianxin Shi; Paul D Shilling; Stanley I Shyn; Jeremy M Silverman; Susan L Slager; Susan L Smalley; Johannes H Smit; Erin N Smith; Edmund J S Sonuga-Barke; David St Clair; Matthew State; Michael Steffens; Hans-Christoph Steinhausen; John S Strauss; Jana Strohmaier; T Scott Stroup; James S Sutcliffe; Peter Szatmari; Szabocls Szelinger; Srinivasa Thirumalai; Robert C Thompson; Alexandre A Todorov; Federica Tozzi; Jens Treutlein; Manfred Uhr; Edwin J C G van den Oord; Gerard Van Grootheest; Jim Van Os; Astrid M Vicente; Veronica J Vieland; John B Vincent; Peter M Visscher; Christopher A Walsh; Thomas H Wassink; Stanley J Watson; Myrna M Weissman; Thomas Werge; Thomas F Wienker; Ellen M Wijsman; Gonneke Willemsen; Nigel Williams; A Jeremy Willsey; Stephanie H Witt; Wei Xu; Allan H Young; Timothy W Yu; Stanley Zammit; Peter P Zandi; Peng Zhang; Frans G Zitman; Sebastian Zöllner; Bernie Devlin; John R Kelsoe; Pamela Sklar; Mark J Daly; Michael C O'Donovan; Nicholas Craddock; Patrick F Sullivan; Jordan W Smoller; Kenneth S Kendler; Naomi R Wray
Journal:  Nat Genet       Date:  2013-08-11       Impact factor: 38.330

10.  Understanding multicellular function and disease with human tissue-specific networks.

Authors:  Casey S Greene; Arjun Krishnan; Aaron K Wong; Emanuela Ricciotti; Rene A Zelaya; Daniel S Himmelstein; Ran Zhang; Boris M Hartmann; Elena Zaslavsky; Stuart C Sealfon; Daniel I Chasman; Garret A FitzGerald; Kara Dolinski; Tilo Grosser; Olga G Troyanskaya
Journal:  Nat Genet       Date:  2015-04-27       Impact factor: 38.330

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  49 in total

Review 1.  Cross-species molecular dissection across alcohol behavioral domains.

Authors:  Sean P Farris; Brien P Riley; Robert W Williams; Megan K Mulligan; Michael F Miles; Marcelo F Lopez; Robert Hitzemann; Ovidiu D Iancu; Alexander Colville; Nicole A R Walter; Priscila Darakjian; Denesa L Oberbeck; James B Daunais; Christina L Zheng; Robert P Searles; Shannon K McWeeney; Kathleen A Grant; R Dayne Mayfield
Journal:  Alcohol       Date:  2017-12-06       Impact factor: 2.405

2.  Tobacco Genomics: Complexity and Translational Challenges.

Authors:  Andrew W Bergen; Elizabeth K Do; Li-Shiun Chen; Sean P David
Journal:  Nicotine Tob Res       Date:  2019-05-21       Impact factor: 4.244

3.  Focus on psychiatric disorders.

Authors: 
Journal:  Nat Neurosci       Date:  2016-10-26       Impact factor: 24.884

4.  Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry.

Authors:  Hon-Cheong So; Carlos Kwan-Long Chau; Wan-To Chiu; Kin-Sang Ho; Cho-Pong Lo; Stephanie Ho-Yue Yim; Pak-Chung Sham
Journal:  Nat Neurosci       Date:  2017-08-14       Impact factor: 24.884

5.  Integrative analyses prioritize GNL3 as a risk gene for bipolar disorder.

Authors:  Qingtuan Meng; Le Wang; Rujia Dai; Jiawen Wang; Zongyao Ren; Sihan Liu; Yan Xia; Yi Jiang; Fangyuan Duan; Kangli Wang; Chunyu Liu; Chao Chen
Journal:  Mol Psychiatry       Date:  2020-08-21       Impact factor: 15.992

6.  Revisiting Antipsychotic Drug Actions Through Gene Networks Associated With Schizophrenia.

Authors:  Karolina Kauppi; Sara Brin Rosenthal; Min-Tzu Lo; Nilotpal Sanyal; Mian Jiang; Ruben Abagyan; Linda K McEvoy; Ole A Andreassen; Chi-Hua Chen
Journal:  Am J Psychiatry       Date:  2018-03-02       Impact factor: 18.112

7.  The value of polygenic analyses in psychiatry.

Authors:  Christel M Middeldorp; Naomi R Wray
Journal:  World Psychiatry       Date:  2018-02       Impact factor: 49.548

8.  Conference Report: Psychiatric Genomics Consortium Meeting: Pathways to Drugs, London, March 2017.

Authors:  Héléna A Gaspar; David A Collier; Daniel H Geschwind; Cathryn M Lewis; Qingqin Li; Bryan L Roth; Patrick F Sullivan; Gerome Breen
Journal:  Biol Psychiatry       Date:  2018-02-08       Impact factor: 13.382

Review 9.  Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual Differences.

Authors:  Ryan Bogdan; David A A Baranger; Arpana Agrawal
Journal:  Annu Rev Clin Psychol       Date:  2018-05-07       Impact factor: 18.561

Review 10.  Precision medicine and pharmacogenetics: what does oncology have that addiction medicine does not?

Authors:  Henry R Kranzler; Rachel V Smith; Robert Schnoll; Afaf Moustafa; Emma Greenstreet-Akman
Journal:  Addiction       Date:  2017-04-21       Impact factor: 6.526

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