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Sci Rep. 2017 Jun 19;7(1):3847. doi: 10.1038/s41598-017-01674-8.

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling.

Collaborators (179)

Boraska Perica V, Franklin CS, Floyd JAB, Thornton LM, Huckins LM, Southam L, Rayner NW, Tachmazidou I, Klump KL, Treasure J, Schmidt U, Tozzi F, Kiezebrink K, Hebebrand J, Gorwood P, Adan RAH, Kas MJH, Favaro A, Santonastaso P, Fernánde-Aranda F, Gratacos M, Rybakowski F, Dmitrzak-Weglarz M, Kaprio J, Keski-Rahkonen A, Raevuori-Helkamaa A, Van Furth EF, Slof-Op't Landt MCT, Hudson JI, Reichborn-Kjennerud T, Knudsen GPS, Monteleone P, Kaplan AS, Karwautz A, Berrettini WH, Schork NJ, Ando T, Inoko H, Esko T, Fischer K, Männik K, Metspalu A, Baker JH, DeSocio JE, Hilliard CE, O'Toole JK, Pantel J, Szatkiewicz JP, Zerwas S, Davis OSP, Helder S, Bühren K, Burghardt R, de Zwaan M, Egberts K, Ehrlich S, Herpertz-Dahlmann B, Herzog W, Imgart H, Scherag A, Zipfel S, Boni C, Ramoz N, Versini A, Danner UN, Hendriks J, Koeleman BPC, Ophoff RA, Strengman E, van Elburg AA, Bruson A, Clementi M, Degortes D, Forzan M, Tenconi E, Docampo E, Escaramís G, Jiménez-Murcia S, Lissowska J, Rajewski A, Szeszenia-Dabrowska N, Slopien A, Hauser J, Karhunen L, Meulenbelt I, Slagboom PE, Tortorella A, Maj M, Dedoussis G, Dikeos D, Gonidakis F, Tziouvas K, Tsitsika A, Papezova H, Slachtova L, Martaskova D, Kennedy JL, Levitan RD, Yilmaz Z, Huemer J, Koubek D, Merl E, Wagner G, Lichtenstein P, Breen G, Cohen-Woods S, Farmer A, McGuffin P, Cichon S, Giegling I, Herms S, Dan Rujescu, Schreiber S, Wichmann HE, Dina C, Sladek R, Gambaro G, Soranzo N, Julia A, Marsal S, Rabionet R, Gaborieau V, Dick DM, Palotie A, Ripatti S, Widén E, Andreassen OA, Espeseth T, Lundervold A, Reinvang I, Steen VM, Le Hellard S, Mattingsdal M, Ntalla I, Bencko V, Foretova L, Janout V, Navratilova M, Gallinger S, Pinto D, Scherer SW, Aschauer H, Carlberg L, Schosser A, Alfredsson L, Ding B, Klareskog L, Padyukov L, Finan C, Kalsi G, Roberts M, Barrett JC, Estivill X, Hinney A, Sullivan PF, Zeggini E, Bulik CM, Brandt H, Crawford S, Crow S, Fichter MM, Halmi KA, Johnson C, Kaplan AS, La Via MC, Mitchell J, Strober M, Rotondo A, Treasure J, Woodside DB, Bulik CM, Keel PK, Klump KL, Lilenfeld L, Thornton LM, Bergen AW, Berrettini W, Kaye W, Magistretti P.

Author information

1
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. lid2@email.chop.edu.
2
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
4
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
5
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. hakonarson@chop.edu.
6
Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. hakonarson@chop.edu.
7
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. hakonarson@chop.edu.

Abstract

We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

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