Article (Scientific journals)
A genome-wide association study of anorexia nervosa.
Boraska, Vesna; Franklin, Christopher S.; Floyd, James A. B. et al.
2014In Molecular Psychiatry, 19 (10), p. 1085-94
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Keywords :
Anorexia Nervosa/genetics; Asian Continental Ancestry Group/genetics; Calcineurin/genetics; Carrier Proteins/genetics; Case-Control Studies; Cullin Proteins/genetics; European Continental Ancestry Group/genetics; Female; Genome-Wide Association Study; Guanine Nucleotide Exchange Factors/genetics; Humans; Japan; Male; Meta-Analysis as Topic; Nuclear Proteins/genetics; Polymorphism, Single Nucleotide
Abstract :
[en] 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=4 x 10(-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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Boraska, Vesna;  Wellcome Trust Sanger Institute
Franklin, Christopher S.;  Wellcome Trust Sanger Institute
Floyd, James A. B.;  Wellcome Trust Sanger Institute
Thornton, Laura M.
Huckins, Laura M.
Southam, Lorraine
Rayner, Nigel William
Tachmazidou, Ioanna
Klump, Kelly L.
Treasure, Janet
Lewis, Cathryn M.
Dedoussis, G.
Dikeos, D.
Gonidakis, F.
Tziouvas, K.
Tsitsika, A.
Papezova, H.
Slachtova, L.
Martaskova, D.
Kennedy, J. L.
Levitan, R. D.
Schmidt, U.
Yilmaz-Ergül, Zeynep ;  Université de Liège > Centre d'études et de rech. sur les macromolécules (CERM)
Huemer, J.
Koubek, D.
Merl, E.
Wagner, G.
Lichtenstein, P.
Breen, G.
Cohen-Woods, S.
Farmer, A.
McGuffin, P.
Tozzi, F.
Cichon, S.
Giegling, I.
Herms, S.
Rujescu, D.
Schreiber, S.
Wichmann, H.-E.
Dina, C.
Sladek, R.
Gambaro, G.
Soranzo, N.
Kiezebrink, K.
Julia, A.
Marsal, S.
Rabionet, R.
Gaborieau, V.
Dick, D. M.
Palotie, A.
Ripatti, S.
Widen, E.
Andreassen, O. A.
Espeseth, T.
Hebebrand, J.
Lundervold, A.
Reinvang, I.
Steen, V. M.
Le Hellard, S.
Mattingsdal, M.
Ntalla, I.
Bencko, V.
Foretova, L.
Janout, V.
Navratilova, M.
Gorwood, P.
Gallinger, S.
Pinto, D.
Scherer, S. W.
Aschauer, H.
Carlberg, L.
Schosser, A.
Alfredsson, L.
Ding, B.
Klareskog, L.
Padyukov, L.
Adan, R. A. H.
Courtet, P.
Guillaume, S.
Jaussent, I.
Finan, C.
Kalsi, G.
Roberts, M.
Logan, D. W.
Peltonen, L.
Ritchie, G. R. S.
Barrett, J. C.
Kas, M. J. H.
Estivill, X.
Hinney, A.
Sullivan, P. F.
Collier, D. A.
Zeggini, E.
Bulik, C. M.
Favaro, A.
Santonastaso, P.
Fernandez-Aranda, F.
Gratacos, M.
Rybakowski, F.
Dmitrzak-Weglarz, M.
Kaprio, J.
Keski-Rahkonen, A.
Raevuori, A.
Van Furth, E. F.
Slof-Op 't Landt, M. C. T.
Hudson, J. I.
Reichborn-Kjennerud, T.
Knudsen, G. P. S.
Monteleone, P.
Kaplan, A. S.
Karwautz, A.
Hakonarson, H.
Berrettini, W. H.
Guo, Y.
Li, D.
Schork, N. J.
Komaki, G.
Ando, T.
Inoko, H.
Esko, T.
Fischer, K.
Mannik, Katrin
Metspalu, A.
Baker, J. H.
Cone, R. D.
Dackor, J.
DeSocio, J. E.
Hilliard, C. E.
O'Toole, J. K.
Pantel, J.
Szatkiewicz, J. P.
Taico, C.
Zerwas, S.
Trace, S. E.
Davis, O. S. P.
Helder, S.
Buhren, K.
Burghardt, R.
de Zwaan, M.
Egberts, K.
Ehrlich, S.
Herpertz-Dahlmann, B.
Herzog, W.
Imgart, H.
Scherag, A.
Scherag, S.
Zipfel, S.
Boni, C.
Ramoz, N.
Versini, A.
Brandys, M. K.
Danner, U. N.
de Kovel, C.
Hendriks, J.
Koeleman, B. P. C.
Ophoff, R. A.
Strengman, E.
van Elburg, Anne-Marie A.
Bruson, Alice
Clementi, Maurizio
Degortes, Daniela
Forzan, Monica
Tenconi, Elodie ;  Université de Liège > Département des sciences de la vie > Centre d'ingénierie des protéines
Docampo Martinez, Elisa ;  Université de Liège - ULiège > Cert.IU.gén.hum.
Escaramis, Geòrgia
Jimenez-Murcia, Susana
Lissowska, Jolanta
Rajewski, Andrzej
Szeszenia-Dabrowska, Neonila
Slopien, Agnieszka
Hauser, Joanna
Karhunen, Leila
Meulenbelt, Ingrid
Slagboom, P. E.
Tortorella, Alfonso
Maj, Mario
More authors (166 more) Less
Language :
English
Title :
A genome-wide association study of anorexia nervosa.
Publication date :
2014
Journal title :
Molecular Psychiatry
ISSN :
1359-4184
eISSN :
1476-5578
Publisher :
Nature Publishing Group, United Kingdom
Volume :
19
Issue :
10
Pages :
1085-94
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 03 March 2016

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