A genome-wide association study of anorexia nervosa

被引：210

作者：

Boraska, V. ^{[1
,2
]}

Franklin, C. S. ^{[1
]}

Floyd, J. A. B. ^{[1
,3
,4
]}

Thornton, L. M. ^{[5
]}

Huckins, L. M. ^{[1
]}

Southam, L. ^{[1
]}

Rayner, N. W. ^{[1
,6
,7
]}

Tachmazidou, I. ^{[1
]}

Klump, K. L. ^{[8
]}

Treasure, J. ^{[9
]}

Lewis, C. M. ^{[10
]}

Schmidt, U. ^{[9
]}

Tozzi, F. ^{[5
]}

Kiezebrink, K. ^{[11
]}

Hebebrand, J. ^{[12
]}

Gorwood, P. ^{[13
,14
]}

Adan, R. A. H. ^{[15
,16
]}

Kas, M. J. H. ^{[15
]}

Favaro, A. ^{[17
]}

Santonastaso, P. ^{[17
]}

Fernandez-Aranda, F. ^{[18
,19
,20
]}

Gratacos, M. ^{[21
,22
,23
,24
]}

Rybakowski, F. ^{[25
]}

Dmitrzak-Weglarz, M. ^{[26
]}

Kaprio, J. ^{[27
,28
,29
]}

Keski-Rahkonen, A. ^{[27
]}

Raevuori, A. ^{[27
,30
]}

Van Furth, E. F. ^{[31
,32
]}

't Landt, M. C. T. Slof-Op ^{[31
,33
]}

Hudson, J. I. ^{[34
]}

Reichborn-Kjennerud, T. ^{[35
,36
]}

Knudsen, G. P. S. ^{[35
]}

Monteleone, P. ^{[37
,38
]}

Kaplan, A. S. ^{[39
,40
]}

Karwautz, A. ^{[41
]}

Hakonarson, H. ^{[42
,43
]}

Berrettini, W. H. ^{[44
]}

Guo, Y. ^{[42
]}

Li, D. ^{[42
]}

Schork, N. J. ^{[45
,46
]}

Komaki, G. ^{[47
,48
]}

Ando, T. ^{[47
]}

Inoko, H. ^{[49
]}

Esko, T. ^{[50
]}

Fischer, K. ^{[50
]}

Maennik, K. ^{[51
,52
]}

Metspalu, A. ^{[50
,51
]}

Baker, J. H. ^{[5
]}

Cone, R. D. ^{[53
]}

Dackor, J. ^{[54
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge, England

[2] Univ Split, Sch Med, Split, Croatia

[3] Queen Mary Univ London, John Vane Sci Ctr, William Harvey Res Inst, London, England

[4] Queen Mary Univ London, John Vane Sci Ctr, London Sch Med & Dent, London, England

[5] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA

[6] WTCHG, Oxford, England

[7] OCDEM, Oxford, England

[8] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA

[9] Kings Coll London, Inst Psychiat, Sect Eating Disorders, London, England

[10] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England

[11] Hlth Serv Res Unit, Aberdeen, Scotland

[12] Univ Duisburg Essen, Univ Klinikum Essen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Essen, Germany

[13] Ctr Psychiat & Neurosci, INSERM U894, Paris, France

[14] Univ Paris 05, St Anne Hosp CMME, Paris, France

[15] Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, Utrecht, Netherlands

[16] Altrecht Eating Disorders Rintveld, Zeist, Netherlands

[17] Univ Padua, Dept Neurosci, Padua, Italy

[18] Univ Hosp Bellvitge IDIBELL, Dept Psychiat, Barcelona, Spain

[19] Univ Hosp Bellvitge IDIBELL, CIBERON, Barcelona, Spain

[20] Univ Barcelona, Sch Med, Dept Clin Sci, Barcelona, Spain

[21] Ctr Genom Regulat CRG, Genom & Dis Grp, Barcelona, Spain

[22] UPF, Barcelona, Spain

[23] Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Barcelona, Spain

[24] Hosp Mar Med Res Inst IMIM, Barcelona, Spain

[25] Inst Psychiat & Neurol, Dept Child & Adolescent Psychiat, Warsaw, Poland

[26] Poznan Univ Med Sci, Dept Psychiat, Poznan, Poland

[27] Univ Helsinki, Hjelt Inst, Helsinki, Finland

[28] Univ Helsinki, Inst Mol Med, Helsinki, Finland

[29] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Helsinki, Finland

[30] Univ Helsinki, Cent Hosp, Dept Adolescent Psychiat, Helsinki, Finland

[31] Ctr Eating Disorders Ursula, Leidschendam, Netherlands

[32] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands

[33] Leiden Univ, Med Ctr, Dept Med Stat, Mol Epidemiol Sect, Leiden, Netherlands

[34] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA

[35] Norwegian Inst Publ Hlth, Dept Genet Environm & Mental Hlth, Oslo, Norway

[36] Univ Oslo, Inst Clin Med, Oslo, Norway

[37] Univ Naples SUN, Dept Psychiat, Naples, Italy

[38] Univ Salerno, Chair Psychiat, I-84100 Salerno, Italy

[39] Ctr Addict & Mental Hlth, Toronto, ON, Canada

[40] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[41] Med Univ Vienna, Dept Child & Adolescent Psychiat, Eating Disorders Unit, Vienna, Austria

[42] Childrens Hosp, Ctr Appl Genom, Philadelphia, PA 19104 USA

[43] Univ Penn, Perelman Sch Med, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA

[44] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[45] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[46] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA

[47] NCNP, NIMH, Dept Psychosomat Res, Tokyo, Japan

[48] Int Univ Hlth & Welf, Sch Hlth Sci, Fukuoka, Japan

[49] Tokai Univ, Dept Mol Life Sci, Kanagawa 2591100, Japan

[50] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

来源：

MOLECULAR PSYCHIATRY | 2014年 / 19卷 / 10期

关键词：

anorexia nervosa; body mass index; eating disorders; genome-wide association study; GWAS; metabolic; POPULATION-BASED TWIN; OF-THE-LITERATURE; BODY-MASS INDEX; EATING-DISORDERS; BULIMIA-NERVOSA; RISK-FACTORS; MEDICAL COMPLICATIONS; ANXIETY DISORDERS; CONTROLLED FAMILY; LINKAGE ANALYSIS;

D O I：

10.1038/mp.2013.187

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

引用

页码：1085 / 1094

页数：10

共 73 条

[1]

Integrating common and rare genetic variation in diverse human populations [J].

Altshuler, David M. ;

Gibbs, Richard A. ;

Peltonen, Leena ;

Dermitzakis, Emmanouil ;

Schaffner, Stephen F. ;

Yu, Fuli ;

Bonnen, Penelope E. ;

de Bakker, Paul I. W. ;

Deloukas, Panos ;

Gabriel, Stacey B. ;

Gwilliam, Rhian ;

Hunt, Sarah ;

Inouye, Michael ;

Jia, Xiaoming ;

Palotie, Aarno ;

Parkin, Melissa ;

Whittaker, Pamela ;

Chang, Kyle ;

Hawes, Alicia ;

Lewis, Lora R. ;

Ren, Yanru ;

Wheeler, David ;

Muzny, Donna Marie ;

Barnes, Chris ;

Darvishi, Katayoon ;

Hurles, Matthew ;

Korn, Joshua M. ;

Kristiansson, Kati ;

Lee, Charles ;

McCarroll, Steven A. ;

Nemesh, James ;

Keinan, Alon ;

Montgomery, Stephen B. ;

Pollack, Samuela ;

Price, Alkes L. ;

Soranzo, Nicole ;

Gonzaga-Jauregui, Claudia ;

Anttila, Verneri ;

Brodeur, Wendy ;

Daly, Mark J. ;

Leslie, Stephen ;

McVean, Gil ;

Moutsianas, Loukas ;

Nguyen, Huy ;

Zhang, Qingrun ;

Ghori, Mohammed J. R. ;

McGinnis, Ralph ;

McLaren, William ;

Takeuchi, Fumihiko ;

Grossman, Sharon R. .

NATURE, 2010, 467 (7311) :52-58

[2]

[Anonymous], 2000, DIAGN STAT MAN MENT, DOI DOI 10.1176/APPI.BOOKS.9780890425787

[3]

Mortality Rates in Patients With Anorexia Nervosa and Other Eating Disorders A Meta-analysis of 36 Studies [J].

Arcelus, Jon ;

Mitchell, Alex J. ;

Wales, Jackie ;

Nielsen, Soren .

ARCHIVES OF GENERAL PSYCHIATRY, 2011, 68 (07) :724-731

[4]

GenABEL: an R library for genome-wide association analysis [J].

Aulchenko, Yurii S. ;

Ripke, Stephan ;

Isaacs, Aaron ;

Van Duijn, Cornelia M. .

BIOINFORMATICS, 2007, 23 (10) :1294-1296

[5]

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates [J].

Bacanu, SA ;

Bulik, CM ;

Klump, K ;

Fichter, MM ;

Halmi, KA ;

Keel, P ;

Kaplan, AS ;

Mitchell, JE ;

Rotondo, A ;

Strober, M ;

Treasure, J ;

Woodside, DB ;

Sonpar, VA ;

Xie, WT ;

Bergen, AW ;

Berrettini, WH ;

Kaye, WH ;

Devlin, B .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2005, 139B (01) :61-68

[6]

Outcomes of eating disorders: A systematic review of the literature [J].

Berkman, Nancy D. ;

Lohr, Kathleen N. ;

Bulik, Cynthia M. .

INTERNATIONAL JOURNAL OF EATING DISORDERS, 2007, 40 (04) :293-309

[7]

The mortality rate from anorexia nervosa [J].

Birmingham, CL ;

Su, J ;

Hlynsky, JA ;

Goldner, EM ;

Gao, M .

INTERNATIONAL JOURNAL OF EATING DISORDERS, 2005, 38 (02) :143-146

[8]

Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits [J].

Boraska, Vesna ;

Davis, Oliver S. P. ;

Cherkas, Lynn F. ;

Helder, Sietske G. ;

Harris, Juliette ;

Krug, Isabel ;

Pei-Chi Liao, Thomas ;

Treasure, Janet ;

Ntalla, Ioanna ;

Karhunen, Leila ;

Keski-Rahkonen, Anna ;

Christakopoulou, Danai ;

Raevuori, Anu ;

Shin, So-Youn ;

Dedoussis, George V. ;

Kaprio, Jaakko ;

Soranzo, Nicole ;

Spector, Tim D. ;

Collier, David A. ;

Zeggini, Eleftheria .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2012, 159B (07) :803-811

[9]

A genome-wide association meta-analysis identifies new childhood obesity loci [J].

Bradfield, Jonathan P. ;

Taal, H. Rob ;

Timpson, Nicholas J. ;

Scherag, Andre ;

Lecoeur, Cecile ;

Warrington, Nicole M. ;

Hypponen, Elina ;

Holst, Claus ;

Valcarcel, Beatriz ;

Thiering, Elisabeth ;

Salem, Rany M. ;

Schumacher, Fredrick R. ;

Cousminer, Diana L. ;

Sleiman, Patrick M. A. ;

Zhao, Jianhua ;

Berkowitz, Robert I. ;

Vimaleswaran, Karani S. ;

Jarick, Ivonne ;

Pennell, Craig E. ;

Evans, David M. ;

St Pourcain, Beate ;

Berry, Diane J. ;

Mook-Kanamori, Dennis O. ;

Hofman, Albert ;

Rivadeneira, Fernando ;

Uitterlinden, Andre G. ;

van Duijn, Cornelia M. ;

van der Valk, Ralf J. P. ;

de Jongste, Johan C. ;

Postma, Dirkje S. ;

Boomsma, Dorret I. ;

Gauderman, W. James ;

Hassanein, Mohamed T. ;

Lindgren, Cecilia M. ;

Magi, Reedik ;

Boreham, Colin A. G. ;

Neville, Charlotte E. ;

Moreno, Luis A. ;

Elliott, Paul ;

Pouta, Anneli ;

Hartikainen, Anna-Liisa ;

Li, Mingyao ;

Raitakari, Olli ;

Lehtimaki, Terho ;

Eriksson, Johan G. ;

Palotie, Aarno ;

Dallongeville, Jean ;

Das, Shikta ;

Deloukas, Panos ;

McMahon, George .

NATURE GENETICS, 2012, 44 (05) :526-+

[10]

Late Onset Eating Disorders in Spain: Clinical Characteristics and Therapeutic Implications [J].

Bueno, B. ;

Krug, I. ;

Bulik, C. M. ;

Jimenez-Murcia, S. ;

Granero, R. ;

Thornton, L. ;

Penelo, E. ;

Menchon, J. M. ;

Sanchez, I. ;

Tinahones, F. J. ;

Fernandez-Aranda, F. .

JOURNAL OF CLINICAL PSYCHOLOGY, 2014, 70 (01) :1-17

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