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. A.H. Adan, C. Boni, R. Cone, G. Dedoussis, E. F. Furth, F. Gonidakis, P. Gorwood, J. Hudson, J. Kaprio, M. Kas, A. Keski-Rahonen, K. Kiezebrink, G. P.S. 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. A. Elburg, Eating Disorders Working Group of the Psychiatric Genomics Consortium, D. A. Collier, P. F. Sullivan, G. Breen, C. M. Bulik, E. Zeggini, S. Cohen-Woods

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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
Publication statusPublished - 1 May 2018

Keywords

  • Genetics
  • molecular biology
  • anorexia nervosa

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