Open Access

Laura M. Huckins, Konstantinos Hatzikotoulas, Lorraine Southam, Laura M. Thornton, Julia Steinberg, Fernando Riveros Mckay Aguilera, Janet Treasure, Ulrike Schmidt, Cerisse Gunasinghe, Anibal Romero, Charles Curtis, Daniel Rhodes, Julie Moens, Gursharan Kalsi, David Dempster, Rufina Leung, Aoife Keohane, Roland Burghardt, Stefan Ehrlich, Johannes Hebebrand, Anke Hinney, Anja Ludolph, Esther Walton, Panos Deloukas, Albert Hofman, Aarno Palotie, Priit Palta, Frank J. A. van Rooij, Kathleen Stirrups, Roger Adan, Claudette Boni, Roger Cone, George Dedoussis, Eric van Furth, Fragiskos Gonidakis, Philip Gorwood, James I. Hudson, Jaakko Kaprio, Martien Kas, Anna Keski-Rahkonen, Kirsty Kiezebrink, Gun Peggy Knudsen, Margarita C. T. Slof-Op ‘t Landt, Mario Maj, Alessio Maria Monteleone, Palmiero Monteleone, Anu Raevuori, Ted Reichborn-Kjennerud, Federica Tozzi, Artemis Tsitsika, Annemarie van Elburg, David A. Collier, Patrick F. Sullivan, Gerome Breen, Cynthia M. Bulik, Eleftheria Zeggini

• 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.