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

Mol Psychiatry. 2018 May;23(5):1169-1180. doi: 10.1038/mp.2017.88. Epub 2017 Jul 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anorexia Nervosa / genetics*
  • Cell Adhesion Molecules / genetics
  • Exome / genetics
  • Family
  • Female
  • GPI-Linked Proteins / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Introns / genetics
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Whites / genetics


  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • OPCML protein, human