American Journal of Psychiatry ( IF 17.7 ) Pub Date : 2017-05-12 , DOI: 10.1176/appi.ajp.2017.16121402 Laramie Duncan 1 , Zeynep Yilmaz 1 , Helena Gaspar 1 , Raymond Walters 1 , Jackie Goldstein 1 , Verneri Anttila 1 , Brendan Bulik-Sullivan 1 , Stephan Ripke 1 , Laura Thornton 1 , Anke Hinney 1 , Mark Daly 1 , Patrick F. Sullivan 1 , Eleftheria Zeggini 1 , Gerome Breen 1 , Cynthia M. Bulik 1 , Laramie Duncan , Zeynep Yilmaz , Héléna Gaspar , Raymond Walters , Jackie Goldstein , Verneri Anttila , Brendan Bulik-Sullivan , Stephan Ripke , Roger Adan , Lars Alfredsson , Tetsuya Ando , Ole Andreassen , Harald Aschauer , Jessica Baker , Jeffrey Barrett , Vladimir Bencko , Andrew Bergen , Wade Berrettini , Andreas Birgegård , Claudette Boni , Vesna Boraska Perica , Harry Brandt , Roland Burghardt , Laura Carlberg , Matteo Cassina , Carolyn Cesta , Sven Cichon , Maurizio Clementi , Sarah Cohen-Woods , Joni Coleman , Roger Cone , Philippe Courtet , Steven Crawford , Scott Crow , Jim Crowley , Unna Danner , Oliver Davis , Martina de Zwaan , George Dedoussis , Daniela Degortes , Janiece DeSocio , Danielle Dick , Dimitris Dikeos , Christian Dina , Bo Ding , Monika Dmitrzak-Weglarz , Elisa Docampo , Karin Egberts , Stefan Ehrlich , Geòrgia Escaramís , Tõnu Esko , Thomas Espeseth , Xavier Estivill , Angela Favaro , Fernando Fernández-Aranda , Manfred Fichter , Chris Finan , Krista Fischer , James Floyd , Manuel Föcker , Lenka Foretova , Monica Forzan , Caroline Fox , Christopher Franklin , Valerie Gaborieau , Steven Gallinger , Giovanni Gambaro , Ina Giegling , Fragiskos Gonidakis , Philip Gorwood , Monica Gratacos , Sébastien Guillaume , Yiran Guo , Hakon Hakonarson , Katherine Halmi , Rebecca Harrison , Konstantinos Hatzikotoulas , Joanna Hauser , Johannes Hebebrand , Sietske Helder , Judith Hendriks , Stefan Herms , Beate Herpertz-Dahlmann , Wolfgang Herzog , Christopher Hilliard , Laura Huckins , James Hudson , Julia Huemer , Hartmut Imgart , Hidetoshi Inoko , Sigrid Jall , Stephane Jamain , Vladimir Janout , Susana Jiménez-Murcia , Craig Johnson , Jenny Jordan , Antonio Julià , Anders Juréus , Gursharan Kalsi , Allan Kaplan , Jaakko Kaprio , Leila Karhunen , Andreas Karwautz , Martien Kas , Walter Kaye , Martin Kennedy , James Kennedy , Anna Keski-Rahkonen , Kirsty Kiezebrink , Youl-Ri Kim , Lars Klareskog , Kelly Klump , Gun Peggy Knudsen , Bobby Koeleman , Doris Koubek , Maria La Via , Mikael Landén , Stephanie Le Hellard , Marion Leboyer , Robert Levitan , Dong Li , Paul Lichtenstein , Lisa Lilenfeld , Jolanta Lissowska , Astri Lundervold , Pierre Magistretti , Mario Maj , Katrin Mannik , Sara Marsal , Debora Kaminska , Nicholas Martin , Morten Mattingsdal , Sara McDevitt , Peter McGuffin , Elisabeth Merl , Andres Metspalu , Ingrid Meulenbelt , Nadia Micali , James Mitchell , Karen Mitchell , Palmiero Monteleone , Alessio Maria Monteleone , Grant Montgomery , Preben Mortensen , Melissa Munn-Chernoff , Timo Müller , Benedetta Nacmias , Marie Navratilova , Ida Nilsson , Claes Norring , Ioanna Ntalla , Roel Ophoff , Julie O’Toole , Aarno Palotie , Jacques Pantel , Hana Papezova , Richard Parker , Dalila Pinto , Raquel Rabionet , Anu Raevuori , Andrzej Rajewski , Nicolas Ramoz , N. William Rayner , Ted Reichborn-Kjennerud , Valdo Ricca , Samuli Ripatti , Franziska Ritschel , Marion Roberts , Alessandro Rotondo , Dan Rujescu , Filip Rybakowski , Paolo Santonastaso , André Scherag , Stephen Scherer , Ulrike Schmidt , Nicholas Schork , Alexandra Schosser , Laura Scott , Jochen Seitz , Lenka Slachtova , Robert Sladek , P. Eline Slagboom , Margarita Slof-Op ’t Landt , Agnieszka Slopien , Tosha Smith , Nicole Soranzo , Sandro Sorbi , Lorraine Southam , Vidar Steen , Eric Strengman , Michael Strober , Jin Szatkiewicz , Neonila Szeszenia-Dabrowska , Ioanna Tachmazidou , Elena Tenconi , Alfonso Tortorella , Federica Tozzi , Janet Treasure , Matthias Tschöp , Artemis Tsitsika , Konstantinos Tziouvas , Annemarie van Elburg , Eric van Furth , Tracey Wade , Gudrun Wagner , Esther Walton , Hunna Watson , H-Erich Wichmann , Elisabeth Widen , D. Blake Woodside , Jack Yanovski , Shuyang Yao , Stephanie Zerwas , Stephan Zipfel , Laura Thornton , Anke Hinney , Mark Daly , Patrick F. Sullivan , Eleftheria Zeggini , Gerome Breen , Cynthia M. Bulik ,
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.
中文翻译：
神经性厌食症的全基因组关联研究显示了重要的基因座和代谢遗传相关性
客观的：
作者对神经性厌食症进行了全基因组关联研究，并计算了与一系列精神病学，教育学和代谢表型的遗传相关性。
方法：在使用1000个基因组计划（第3期）对12例病例对照队列（包括3495例神经性厌食症病例和10982例对照）进行统一的质量控制和归因程序后，作者进行了标准关联分析，然后进行了跨队列的荟萃分析。连锁不平衡得分回归用于计算全基因组通用变异性（基于单核苷酸多态性[SNP]的遗传性[h 2 SNP ]），分区遗传性以及神经性厌食症和其他159种表型之间的遗传相关性（r g）。
结果：获得了10,641,224个SNP和插入缺失变异体的结果，次要等位基因频率> 1％，插补质量得分> 0.6。神经性厌食症的h 2 SNP为0.20（SE = 0.02），表明双胞胎遗传力的很大一部分来自共同的遗传变异。这组作者在一个藏有先前报道的1型糖尿病和自身免疫性疾病基因座的区域中，在第12号染色体上发现了一个全基因组的重要基因座（rs4622308）。神经性厌食症和精神分裂症，神经质，教育程度和高密度脂蛋白胆固醇之间存在显着的正遗传相关性，神经性厌食症与体重指数，胰岛素，葡萄糖和脂质表型之间存在显着的负相关性。
结论：神经性厌食症是一种复杂的可遗传表型，为此，该研究发现了第一个全基因组范围内的重要基因座。神经性厌食症还具有与精神病学表型和代谢性状的巨大且显着的遗传相关性。这项研究结果鼓励将这种经常致命的疾病重新认识为精神病和代谢病因。
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