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

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

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Springer Nature [academic journals on nature.com], Molecular Psychiatry, 5(23), p. 1169-1180, 2017

DOI: 10.1038/mp.2017.88

Springer Nature [academic journals on nature.com], Molecular Psychiatry, 9(23), p. 1969-1969, 2017

DOI: 10.1038/mp.2017.202

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

Journal article published in 2017 by L. M. Huckins, F. J. A. van Rooij, L. M. Thornton, Huckins Lm, K. Hatzikotoulas

, L. Southam, J. Steinberg, F. Aguilera-Mckay, V. Boraska Perica, J. Treasure, U. Schmidt, A. Hofman, C. Gunasinghe, D. Rhodes, M. de Zwaan and other authors.

This paper is made freely available by the publisher.

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Abstract

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.

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

Abstract