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


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.

DOI: 10.1038/ng.2711

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@article{Lee2013GeneticRB, title={Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs}, author={Sang Hong Lee and Stephan Ripke and Benjamin M. Neale and Stephen V Faraone and Shaun M Purcell and Roy H. Perlis and B. J. Mowry and Anita Thapar and M. E. Goddard and John S. Witte and Devin M Absher and Ingrid Agartz and Huda Akil and Farooq Amin and Ole A. Andreassen and Adebayo Anjorin and Richard J. L. Anney and Verneri Anttila and Dan E Arking and Philip Asherson and Maria Helena Pinto de Azevedo and Lena Backlund and Judith A. Badner and Anthony Bailey and Tobias Banaschewski and Jack David Barchas and Michael R. Barnes and Thomas B. Barrett and Nicholas James Bass and Agatino Battaglia and Michael Bauer and M{\'o}nica Bay{\'e}s and Frank Bellivier and Sarah E Bergen and Wade H. Berrettini and Catalina Betancur and Thomas Bettecken and Joseph Biederman and Elisabeth B. Binder and Donald Wayne Black and Douglas Blackwood and Cinnamon S. Bloss and Michael Boehnke and Dorret I. Boomsma and Gerome Breen and Ren{\'e} Breuer and Richard Bruggeman and Paul Cormican and Nancy G. Buccola and Jan K. Buitelaar and William E. Bunney and Joseph D. Buxbaum and William Byerley and Enda M. Byrne and Sian Caesar and Wiepke Cahn and Rita M. Cantor and Miquel Casas and Aravinda Chakravarti and Kimberly Chambert and Khalid Choudhury and Sven Cichon and Claude Robert Cloninger and David A. Collier and Edwin H. Cook and Hilary H. Coon and Bru Cormand and Aiden P. Corvin and William H. Coryell and David W. Craig and Ian W. Craig and Jennifer Crosbie and Michael L. Cuccaro and David Curtis and Darina Czamara and S. R. Datta and Geraldine Dawson and Richard K. Day and Eco J de Geus and Franziska Degenhardt and Srdjan Djurovic and Gary Donohoe and Alysa E. Doyle and Jubao Duan and Frank Dudbridge and Eftichia Duketis and Richard P. Ebstein and Howard J. Edenberg and Josephine Elia and Sean Ennis and B Etain and Ayman H. Fanous and Anne Farmer and I. Nicol Ferrier and Matthew Flickinger and {\'E}ric Fombonne and Tatiana Foroud and Josef Frank and Barbara Franke and Christine H Fraser and Robert Freedman and Nelson B. Freimer and Christine M. Freitag and Marion Friedl and Louise Fris{\'e}n and Louise P Gallagher and Pablo V. Gejman and Lyudmila Georgieva and Elliot S. Gershon and Daniel H. Geschwind and Ina Giegling and Michael Gill and Scott D Gordon and Katherine Gordon-Smith and Elaine K Green and Tiffany A. Greenwood and Dorothy E. Grice and Magdalena M Gross and Detelina Grozeva and Weihua Guan and Hugh Malcolm Douglas Gurling and L D Dick de Haan and Jonathan L. Haines and Hakon Hakonarson and Joachim F. Hallmayer and Steven P. Hamilton and Marian L. Hamshere and Thomas Folkmann Hansen and Annette M Hartmann and Martin Hautzinger and A Christopher Heath and Anjali K. Henders and Stefan Herms and Ian B. Hickie and Maria Mananita S Hipolito and Susanne Hoefels and Peter Holmans and Florian Holsboer and Witte J. G. Hoogendijk and Jouke-Jan Hottenga and Christina M. Hultman and Vanessa H. Hus and Andr{\'e}s Ingason and Marcus Ising and St{\'e}phane Jamain and Edward G. Jones and Ian Jones and Lisa Anne Jones and Jung-Ying Tzeng and Anna K. K{\"a}hler and Ren{\'e} S. Kahn and Radhika Kandaswamy and Matthew C. Keller and James L. Kennedy and Elaine Kenny and Lindsey S Kent and Yunjung Kim and George K Kirov and Sabine M Klauck and Lambertus L Klei and James A. Knowles and Martin A. Kohli and Daniel L. Koller and Bettina Konte and Ania Korszun and L. C. Krabbendam and Robert Krasucki and Jonna Kuntsi and Phoenix Kwan and Mikael Land{\'e}n and Niklas L{\aa}ngstr{\"{o}m and Mark Lathrop and Jacob Lawrence and William Lawson and Marion Leboyer and David H. Ledbetter and Phil H. Lee and Todd Lencz and Klaus-Peter Lesch and Douglas F. Levinson and Cathryn M. Lewis and Jun Li and Paul Lichtenstein and Jeffrey A. Lieberman and Dan-Yu Lin and Don H. Linszen and Chunyu Liu and Falk W. Lohoff and Sandra K. Loo and Catherine Lord and Jennifer K. Lowe and Susanne Lucae and Donald J Macintyre and Pamela A. F. Madden and Elena Maestrini and Patrik K. E. Magnusson and Pamela B. Mahon and Wolfgang Maier and Anil K. Malhotra and Shrikant M. Mane and Christa L. Martin and Nicholas G. Martin and Manuel Mattheisen and Keith Matthews and Morten Mattingsdal and Steven A. McCarroll and Kevin A. McGhee and James J. McGough and Patrick J. McGrath and Peter McGuffin and Melvin G. McInnis and Andrew M. McIntosh and Rebecca Mckinney and Alan W McLean and Francis J. McMahon and William McMahon and Q Li and Helena Medeiros and Sarah E. Medland and Sandra Meier and Ingrid Melle and Fan Meng and Jobst Meyer and Christel M Middeldorp and Lefkos T. Middleton and Vihra K Milanova and Ana Luisa P. de Miranda and Anthony P. Monaco and Grant W. Montgomery and Jennifer L. 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O'Donovan and Nicholas J Craddock and Patrick F. Sullivan and Jordan W. Smoller and Kenneth S. Kendler and Naomi R Wray}, journal={Nature Genetics}, year={2013}, volume={45}, pages={984-994} }