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

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

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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, M. de Zwaan, F. J. A. van Rooij, E. van Furth, A. A. van Elburg, E. F. van Furth

, A. van Elburg, S. Zerwas, S. Zipfel, L. M. Thornton, M. C. T. Slof-Op ’T Landt, D. Rhodes, J. Moens, V. Boraska Perica, P. F. Sullivan and other authors.

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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