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

Hong Lee 1 Stephan Ripke 2, 3 Benjamin Neale 3, 2 Stephen Faraone 4, 5 Shaun Purcell 2, 3, 6 Roy Perlis 2, 7, 8 Bryan Mowry 1, 9 Anita Thapar 10, 11 Michael Goddard 12, 13 John Witte 14 Devin Absher 15 Ingrid Agartz 16 Huda Akil 17 Farooq Amin 18 Ole Andreassen 16, 19 Adebayo Anjorin 18, 20 Richard Anney 21 Verneri Anttila 3 Dan Arking 22 Philip Asherson 23 Maria Azevedo 24 Lena Backlund 21 Judith Badner 25 Anthony Bailey 26 Tobias Banaschewski 27 Jack Barchas 28 Michael Barnes 29 Thomas Barrett 30 Nicholas Bass 20 Agatino Battaglia 31 Michael Bauer 32 Mònica Bayés 33 Frank Bellivier 34 Sarah Bergen 2, 8 Wade Berrettini 35 Catalina Betancur 36 Thomas Bettecken 37 Joseph Biederman 38 Elisabeth Binder 39 Donald Black 40 Douglas Blackwood 41, 42 Cinnamon Bloss 43 Michael Boehnke 44 Dorret Boomsma 45, 46 Gerome Breen 23, 47, 48 René Breuer 49 Richard Bruggeman 50 Paul Cormican 21 Nancy Buccola 51 Jan Buitelaar 52 William Bunney 53 Joseph Buxbaum 54, 55, 56, 57, 58, 59, 60 William Byerley 61 Enda Byrne 1 Sian Caesar 62 Wiepke Cahn 56 Rita Cantor 63 Miguel Casas 56 Aravinda Chakravarti 22, 46 Kimberly Chambert 2 Khalid Choudhury 20 Sven Cichon 64, 65, 66 Robert Cloninger 56 David Collier 23, 48, 67 Edwin Cook 68 Hilary Coon 69 Bru Cormand 56 Aiden Corvin 21, 70 William Coryell 40 David Craig 71 Ian Craig 23 Jennifer Crosbie 71 Michael Cuccaro 72 David Curtis 73 Darina Czamara 74 Susmita Datta 75 Geraldine Dawson 76 Richard Day 77 Eco de Geus 78 Franziska Degenhardt 64, 65 Srdjan Djurovic 16, 79 Gary Donohoe 21, 80 Alysa Doyle 81 Jubao Duan 82 Frank Dudbridge 83 Eftichia Duketis 84 Richard Ebstein 85 Howard Edenberg 86 Josephine Elia 71 Sean Ennis 87 Bruno Etain 34, 88 Ayman Fanous 89 Anne Farmer 23, 48 I Nicol Ferrier 90 Matthew Flickinger 91 Eric Fombonne 92 Tatiana Foroud 93 Josef Frank 94 Barbara Franke 94 Christine Fraser 10, 11 Robert Freedman 95 Nelson Freimer 96 Christine Freitag 84 Marion Friedl 97 Louise Frisén 98 Louise Gallagher 21 Pablo Gejman 82 Lyudmila Georgieva 10, 11 Elliot Gershon 25 Daniel Geschwind 99 Ina Giegling 97 Michael Gill 21 Scott Gordon 94 Katherine Gordon-Smith 11, 62, 100 Elaine Green 100 Tiffany Greenwood 71 Dorothy Grice 101 Magdalena Gross 102 Detelina Grozeva 11, 100 Weihua Guan 91, 102 Hugh Gurling 20 Lieuwe de Haan 101 Jonathan Haines 103 Hakon Hakonarson 104, 105 Joachim Hallmayer 106 Steven Hamilton 107 Marian Hamshere 11, 100, 108 Thomas Hansen 109 Annette Hartmann 97 Martin Hautzinger 110 Andrew Heath 46 Anjali Henders 101 Stefan Herms 97 Ian Hickie 111 Maria Hipolito 94 Susanne Hoefels 101 Peter Holmans 112, 11 Florian Holsboer 113 Witte Hoogendijk 114 Jouke-Jan Hottenga 46 Christina Hultman 115 Vanessa Hus 116 Andrés Ingason 109 Marcus Ising 37 Stéphane Jamain 34 Edward Jones 117 Ian Jones 10, 11 Lisa Jones 62 Jung-Ying Tzeng 118 Anna Kähler 119 René Kahn 120, 121 Radhika Kandaswamy 18, 20 Matthew Keller 119 James Kennedy 122 Elaine Kenny 21, 80 Lindsey Kent 123 Yunjung Kim 118 George Kirov 10, 11, 124 Sabine Klauck 125 Lambertus Klei 101 James Knowles 126 Martin Kohli 37 Daniel Koller 93 Bettina Konte 78 Ania Korszun 100 Lydia Krabbendam 119 Robert Krasucki 20 Jonna Kuntsi 23 Phoenix Kwan 91 Mikael Landén 115, 127 Niklas Långström 127 Mark Lathrop 128 Jacob Lawrence 18, 20 William Lawson 94 Marion Leboyer 34, 88 David Ledbetter 129 Phil Lee 8 Todd Lencz 6 Klaus-Peter Lesch 130 Douglas Levinson 129 Cathryn Lewis 23, 100, 131 Jun Li 132 Paul Lichtenstein 115 Jeffrey Lieberman 130 Dan-Yu Lin 118 Don Linszen 130 Chunyu Liu 118 Falk Lohoff 35 Sandra Loo 118 Catherine Lord 116 Jennifer Lowe 102 Susanne Lucae 133 Donald Macintyre 129 Pamela Madden 78 Elena Maestrini 134 Patrik Magnusson 135 Pamela Mahon 136 Wolfgang Maier 135 Anil Malhotra 6 Shrikant Mane 137 Christa Martin 138 Nicholas Martin 45, 139 Manuel Mattheisen 65, 140 Keith Matthews 90 Morten Mattingsdal 16, 141, 142 Steven Mccarroll 2 Kevin Mcghee 41, 42 James Mcgough 138 Patrick Mcgrath 138 Peter Mcguffin 23, 48 Melvin Mcinnis 143 Andrew Mcintosh 41, 42 Rebecca Mckinney 71 Alan Mclean 41, 42 Francis Mcmahon 144, 80 William Mcmahon 69 Andrew Mcquillin 20 Helena Medeiros 145 Sarah Medland 78 Sandra Meier 49 Ingrid Melle 16, 19, 141, 146 Fan Meng 17 Jobst Meyer 138 Christel Middeldorp 46 Lefkos Middleton 147 Vihra Milanova 148 Ana Miranda 149 Anthony Monaco 150 Grant Montgomery 45, 139 Jennifer Moran 2 Daniel Moreno-De-Luca 36 Gunnar Morken 119, 151 Derek Morris 21, 70 Eric Morrow 152, 153 Valentina Moskvina 11, 124 Pierandrea Muglia 108 Thomas Mühleisen 65, 64 Walter Muir 41, 42 Bertram Müller-Myhsok 154 Michael Murtha 130 Richard Myers 15 Inez Myin-Germeys 133 Michael Neale 89 Stan Nelson 130 Caroline Nievergelt 71 Ivan Nikolov 10, 11 Vishwajit Nimgaonkar 155 Willem Nolen 156 Markus Nöthen 124, 130 John Nurnberger 93 Evaristus Nwulia 94 Dale Nyholt 78 Colm O'Dushlaine 2 Robert Oades 133 Ann Olincy 95 Guiomar Oliveira 24, 145 Line Olsen 89, 109 Roel Ophoff 121 Urban Osby 98 Michael Owen 10, 11 Aarno Palotie 157 Jeremy Parr 138 Andrew Paterson 158, 159 Carlos Pato 89 Michele Pato 89 Brenda Penninx 45 Michele Pergadia 78 Margaret Pericak-Vance 72 Benjamin Pickard 41, 42 Jonathan Pimm 20 Joseph Piven 160 Danielle Posthuma 112 James Potash 161, 162 Fritz Poustka 84 Peter Propping 65 Vinay Puri 20 Digby Quested 95 Emma Quinn 6, 21, 70 Josep Antoni Ramos-Quiroga 56 Henrik Rasmussen 56, 109 Soumya Raychaudhuri 2, 3 Karola Rehnström 163 Andreas Reif 164 Marta Ribasés 95 John Rice 165 Marcella Rietschel 49 Kathryn Roeder 166 Herbert Roeyers 167 Lizzy Rossin 2 Aribert Rothenberger 168 Guy Rouleau 169 Douglas Ruderfer 6 Dan Rujescu 97 Alan Sanders 82 Stephan Sanders 170 Susan Santangelo 171, 172 Joseph Sergeant 173 Russell Schachar 56 Martin Schalling 98 Alan Schatzberg 174 William Scheftner 163 Gerard Schellenberg 175 Stephen Scherer 158, 159 Nicholas Schork 176 Thomas Schulze 49, 80, 161, 177 Johannes Schumacher 65 Markus Schwarz 178 Edward Scolnick 2 Laura Scott 91 Jianxin Shi 179 Paul Shilling 71 Stanley Shyn 56 Jeremy Silverman 101 Susan Slager 56 Susan Smalley 56 Johannes Smit 45, 78 Erin Smith 43 Edmund Sonuga-Barke 129, 180 David St Clair 47 Matthew State 130 Michael Steffens 140 Hans-Christoph Steinhausen 181 John Strauss 182 Jana Strohmaier 49 Scott Stroup 95 James Sutcliffe 103, 183, 184 Peter Szatmari 185 Szabocls Szelinger 186 Srinivasa Thirumalai 187 Robert Thompson 17, 53 Alexandre Todorov 188 Federica Tozzi 108 Jens Treutlein 163 Manfred Uhr 37 Edwin van den Oord 56 Gerard van Grootheest 130 Jim van Os 130 Astrid Vicente 189, 190 Veronica Vieland 191 John Vincent 192 Peter Visscher 1 Christopher Walsh 109 Thomas Wassink 193 Stanley Watson 17 Myrna Weissman 135 Thomas Werge 109 Thomas Wienker 97, 140 Ellen Wijsman 194 Gonneke Willemsen 45 Nigel Williams 10, 11 Jeremy Willsey 130 Stephanie Witt 49 Wei Xu 195 Allan Young 90, 196 Timothy Yu 56 Stanley Zammit 10, 11 Peter Zandi 197 Peng Zhang 198 Frans Zitman 78 Sebastian Zöllner 143 Bernie Devlin 101 John Kelsoe 199, 200 Pamela Sklar 6 Mark Daly 2, 3 Michael O'Donovan 10, 11 Nicholas Craddock 11, 10 Patrick Sullivan 78 Jordan Smoller 2, 8 Kenneth Kendler 6 Naomi Wray 1, *
* Corresponding author
Abstract : Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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Hong Lee, Stephan Ripke, Benjamin Neale, Stephen Faraone, Shaun Purcell, et al.. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.. Nature Genetics, Nature Publishing Group, 2013, 45 (9), pp.984-94. ⟨10.1038/ng.2711⟩. ⟨inserm-00864642⟩

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