OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.
OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoproteincholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. CONCLUSIONS:Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.
Authors: Brendan K Bulik-Sullivan; Po-Ru Loh; Hilary K Finucane; Stephan Ripke; Jian Yang; Nick Patterson; Mark J Daly; Alkes L Price; Benjamin M Neale Journal: Nat Genet Date: 2015-02-02 Impact factor: 38.330
Authors: M Föcking; L M Lopez; J A English; P Dicker; A Wolff; E Brindley; K Wynne; G Cagney; D R Cotter Journal: Mol Psychiatry Date: 2014-07-22 Impact factor: 15.992
Authors: Andréa Poyastro Pinheiro; Laura M Thornton; Katherine H Plotonicov; Federica Tozzi; Kelly L Klump; Wade H Berrettini; Harry Brandt; Steven Crawford; Scott Crow; Manfred M Fichter; David Goldman; Katherine A Halmi; Craig Johnson; Allan S Kaplan; Pamela Keel; Maria LaVia; James Mitchell; Alessandro Rotondo; Michael Strober; Janet Treasure; D Blake Woodside; Ann Von Holle; Robert Hamer; Walter H Kaye; Cynthia M Bulik Journal: Int J Eat Disord Date: 2007-07 Impact factor: 4.861
Authors: Iris E Sommer; Roos van Westrhenen; Marieke J H Begemann; Lot D de Witte; Stefan Leucht; René S Kahn Journal: Schizophr Bull Date: 2013-10-08 Impact factor: 9.306
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: Laura A Berner; Tiffany A Brown; Jason M Lavender; Emily Lopez; Christina E Wierenga; Walter H Kaye Journal: Mol Cell Endocrinol Date: 2018-11-02 Impact factor: 4.102
Authors: Alia A Hussain; Christopher Hübel; Mathias Hindborg; Emilie Lindkvist; Annie M Kastrup; Zeynep Yilmaz; René K Støving; Cynthia M Bulik; Jan M Sjögren Journal: Int J Eat Disord Date: 2019-03-28 Impact factor: 4.861
Authors: Alicia R Martin; Mark J Daly; Elise B Robinson; Steven E Hyman; Benjamin M Neale Journal: Biol Psychiatry Date: 2018-12-28 Impact factor: 13.382
Authors: Laura M Thornton; Melissa A Munn-Chernoff; Jessica H Baker; Anders Juréus; Richard Parker; Anjali K Henders; Janne T Larsen; Liselotte Petersen; Hunna J Watson; Zeynep Yilmaz; Katherine M Kirk; Scott Gordon; Virpi M Leppä; Felicity C Martin; David C Whiteman; Catherine M Olsen; Thomas M Werge; Nancy L Pedersen; Walter Kaye; Andrew W Bergen; Katherine A Halmi; Michael Strober; Allan S Kaplan; D Blake Woodside; James Mitchell; Craig L Johnson; Harry Brandt; Steven Crawford; L John Horwood; Joseph M Boden; John F Pearson; Laramie E Duncan; Jakob Grove; Manuel Mattheisen; Jennifer Jordan; Martin A Kennedy; Andreas Birgegård; Paul Lichtenstein; Claes Norring; Tracey D Wade; Grant W Montgomery; Nicholas G Martin; Mikael Landén; Preben Bo Mortensen; Patrick F Sullivan; Cynthia M Bulik Journal: Contemp Clin Trials Date: 2018-10-01 Impact factor: 2.226