Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

L. M. Huckins, K. Hatzikotoulas, L. Southam, L. M. Thornton, J. Steinberg, F. Aguilera-Mckay, J. Treasure, U. Schmidt, C. Gunasinghe, A. Romero, C. Curtis, D. Rhodes, J. Moens, G. Kalsi, D. Dempster, R. Leung, A. Keohane, R. Burghardt, S. Ehrlich, J. HebebrandA. Hinney, A. Ludolph, E. Walton, P. Deloukas, A. Hofman, A. Palotie, P. Palta, F. J.A. van Rooij, K. Stirrups, R. Adan, C. Boni, R. Cone, G. Dedoussis, E. van Furth, F. Gonidakis, P. Gorwood, J. Hudson, J. Kaprio, M. Kas, A. Keski-Rahonen, K. Kiezebrink, G. P. Knudsen, M. C.T. Slof-Op ’T Landt, M. Maj, A. M. Monteleone, P. Monteleone, A. H. Raevuori, T. Reichborn-Kjennerud, F. Tozzi, A. Tsitsika, A. Elburg, D. A. Collier, P. F. Sullivan, G. Breen, C. M. Bulik, E. Zeggini, R. A.H. Adan, L. Alfredsson, T. Ando, O. A. Andreassen, H. Aschauer, J. H. Baker, J. C. Barrett, V. Bencko, A. W. Bergen, W. H. Berrettini, A. Birgegård, C. Boni, V. Boraska Perica, H. Brandt, C. M. Bulik, L. Carlberg, M. Cassina, S. Cichon, M. Clementi, S. Cohen-Woods, J. Coleman, R. D. Cone, P. Courtet, S. Crawford, S. Crow, J. Crowley, U. N. Danner, O. S.P. Davis, M. Zwaan, G. Dedoussis, D. Degortes, J. E. Desocio, D. M. Dick, D. Dikeos, C. Dina, B. Ding, M. Dmitrzak-Weglarz, E. Docampo, L. Duncan, K. Egberts, G. Escaramís, T. Esko, T. Espeseth, X. Estivill, A. Favaro, F. Fernández-Aranda, M. M. Fichter, C. Finan, K. Fischer, J. A.B. Floyd, L. Foretova, M. Forzan, C. S. Franklin, S. Gallinger, G. Gambaro, H. A. Gaspar, I. Giegling, F. Gonidakis, P. Gorwood, M. Gratacos, S. Guillaume, Y. Guo, H. Hakonarson, K. A. Halmi, K. Hatzikotoulas, J. Hauser, J. Hebebrand, S. Helder, S. Herms, B. Herpertz-Dahlmann, W. Herzog, C. E. Hilliard, C. Hübel, L. M. Huckins, J. I. Hudson, J. Huemer, H. Inoko, V. Janout, S. Jiménez-Murcia, C. Johnson, A. Julià, A. Juréus, G. Kalsi, D. Kaminska, A. S. Kaplan, L. Karhunen, A. Karwautz, M. J.H. Kas, W. Kaye, J. L. Kennedy, A. Keski-Rahkonen, K. Kiezebrink, L. Klareskog, K. L. Klump, G. P.S. Knudsen, B. P.C. Koeleman, D. Koubek, MC C.L. Via, M. Landén, S. Le Hellard, R. D. Levitan, D. Li, P. Lichtenstein, L. Lilenfeld, J. Lissowska, A. Lundervold, P. Magistretti, K. Mannik, S. Marsal, N. Martin, M. Mattingsdal, S. McDevitt, P. McGuffin, E. Merl, A. Metspalu, I. Meulenbelt, N. Micali, J. Mitchell, K. Mitchell, P. Mortensen, M. A. Munn-Chernoff, M. Navratilova, I. Nilsson, C. Norring, I. Ntalla, R. A. Ophoff, J. K. O'toole, J. Pantel, H. Papezova, D. Pinto, R. Rabionet, A. Raevuori, A. Rajewski, N. Ramoz, N. W. Rayner, T. Reichborn-Kjennerud, S. Ripatti, M. Roberts, A. Rotondo, D. Rujescu, F. Rybakowski, P. Santonastaso, A. Scherag, S. W. Scherer, U. Schmidt, N. J. Schork, A. Schosser, L. Slachtova, R. Sladek, P. E. Slagboom, A. Slopien, N. Soranzo, L. Southam, V. M. Steen, E. Strengman, M. Strober, J. P. Szatkiewicz, N. Szeszenia-Dabrowska, I. Tachmazidou, E. Tenconi, L. M. Thornton, A. Tortorella, F. Tozzi, K. Tziouvas, A. A. Elburg, E. F. Furth, G. Wagner, E. Walton, H. Watson, H. E. Wichmann, E. Widen, D. B. Woodside, J. Yanovski, S. Yao, Z. Yilmaz, E. Zeggini, S. Zerwas, S. Zipfel

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30 Scopus citations

Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6), and rs7700147, an intergenic variant (P=2.93 × 10 -5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Original languageEnglish
Pages (from-to)1169-1180
Number of pages12
JournalMolecular Psychiatry
Volume23
Issue number5
DOIs
StatePublished - 1 May 2018
Externally publishedYes

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