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

Research output: Contribution to journalArticle

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 Hebebrand & 31 more A 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, G Breen, Eating Disorder Working Group of the Psychiatric Genomics Consortium

Original languageEnglish
Pages (from-to)1169–1180
JournalMolecular Psychiatry
Volume23
Issue number5
Early online date25 Jul 2017
DOIs
Accepted/In press17 Feb 2017
E-pub ahead of print25 Jul 2017
Published2018

King's Authors

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.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.

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