Thomas H McCoy1, Victor M Castro2, Kamber L Hart2, Amelia M Pellegrini2, Sheng Yu3, Tianxi Cai4, Roy H Perlis2. 1. Center for Quantitative Health and Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: thmccoy@partners.org. 2. Center for Quantitative Health and Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. Tsinghua University, Beijing, China. 4. Harvard School of Public Health, Boston, Massachusetts.
Abstract
BACKGROUND: Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown. METHODS: We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits. RESULTS: Among 4687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S for arousal (p = 2.29 × 10-8) and one spanning the FPR3 gene for cognition (p = 3.22 × 10-8). CONCLUSIONS: Natural language processing identifies dimensional phenotypes that may facilitate the discovery of common genetic variation that is relevant to psychopathology.
BACKGROUND: Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown. METHODS: We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits. RESULTS: Among 4687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S for arousal (p = 2.29 × 10-8) and one spanning the FPR3 gene for cognition (p = 3.22 × 10-8). CONCLUSIONS: Natural language processing identifies dimensional phenotypes that may facilitate the discovery of common genetic variation that is relevant to psychopathology.
Authors: Thomas Insel; Bruce Cuthbert; Marjorie Garvey; Robert Heinssen; Daniel S Pine; Kevin Quinn; Charles Sanislow; Philip Wang Journal: Am J Psychiatry Date: 2010-07 Impact factor: 18.112
Authors: Thomas H McCoy; Victor M Castro; Hannah R Rosenfield; Andrew Cagan; Isaac S Kohane; Roy H Perlis Journal: Am J Psychiatry Date: 2015-04 Impact factor: 18.112
Authors: Victor M Castro; Jessica Minnier; Shawn N Murphy; Isaac Kohane; Susanne E Churchill; Vivian Gainer; Tianxi Cai; Alison G Hoffnagle; Yael Dai; Stefanie Block; Sydney R Weill; Mireya Nadal-Vicens; Alisha R Pollastri; J Niels Rosenquist; Sergey Goryachev; Dost Ongur; Pamela Sklar; Roy H Perlis; Jordan W Smoller Journal: Am J Psychiatry Date: 2014-12-12 Impact factor: 18.112
Authors: Brenna M Henn; Lawrence Hon; J Michael Macpherson; Nick Eriksson; Serge Saxonov; Itsik Pe'er; Joanna L Mountain Journal: PLoS One Date: 2012-04-03 Impact factor: 3.240
Authors: Christopher C Chang; Carson C Chow; Laurent Cam Tellier; Shashaank Vattikuti; Shaun M Purcell; James J Lee Journal: Gigascience Date: 2015-02-25 Impact factor: 6.524
Authors: Vivian S Gainer; Andrew Cagan; Victor M Castro; Stacey Duey; Bhaswati Ghosh; Alyssa P Goodson; Sergey Goryachev; Reeta Metta; Taowei David Wang; Nich Wattanasin; Shawn N Murphy Journal: J Pers Med Date: 2016-02-26
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
Authors: Thomas H McCoy; Larry Han; Amelia M Pellegrini; Rudolph E Tanzi; Sabina Berretta; Roy H Perlis Journal: Alzheimers Dement Date: 2020-01-16 Impact factor: 21.566
Authors: Kamber L Hart; Amelia M Pellegrini; Brent P Forester; Sabina Berretta; Shawn N Murphy; Roy H Perlis; Thomas H McCoy Journal: Gen Hosp Psychiatry Date: 2020-11-10 Impact factor: 3.238
Authors: Valerio Napolioni; Marzia A Scelsi; Raiyan R Khan; Andre Altmann; Michael D Greicius Journal: Front Genet Date: 2021-01-29 Impact factor: 4.599