1. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa
- Author
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Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Slof-Op 't Landt, M C T, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, Collier, D A, Sullivan, P F, Breen, G, Bulik, C M, and Zeggini, E
- 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.
- Published
- 2018
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