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

by L.M. Huckins, K. Hatzikotoulas, L. Southam, L.M. Thornton, (...), P.F. Sullivan, G. Breen, C.M. Bulik, E. Zeggini
Year: 2017 ISSN: DOI: 10.1038/mp.2017.88

Bibliography

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, (…), A.H. Raevuori, T. Reichborn-Kjennerud, F. Tozzi, A. Tsitsika, A. van Elburg, Eating Disorder Working Group of the Psychiatric Genomics Consortium, D.A. Collier, P.F. Sullivan, G. Breen, C.M. Bulik and E. Zeggini
Molecular Psychiatry, 2017

Abstract

Pub_ICL_2017Anorexia 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.

Keywords

Anorexia nervosa Neuropsychiatric disorders Body weight GWAS