You are here

Mol Psychiatry DOI:10.1038/mp.2017.88

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

Publication TypeJournal Article
Year of Publication2018
AuthorsHuckins, LM, Hatzikotoulas, K, Southam, L, Thornton, LM, 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, FJA, 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, Landt, MCTSlof-O, Maj, M, Monteleone, AM, Monteleone, P, Raevuori, AH, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, Collier, DA, Sullivan, PF, Breen, G, Bulik, CM, Zeggini, E
Corporate AuthorsEating Disorder Working Group of the Psychiatric Genomics Consortium
JournalMol Psychiatry
Volume23
Issue5
Pages1169-1180
Date Published2018 May
ISSN1476-5578
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), and rs7700147, an intergenic variant (P=2.93 × 10). 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.

DOI10.1038/mp.2017.88
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29155802?dopt=Abstract

Alternate JournalMol. Psychiatry
PubMed ID29155802
PubMed Central IDPMC5828108
Grant ListP50 AG005138 / AG / NIA NIH HHS / United States
R01 MH097276 / MH / NIMH NIH HHS / United States
P50 MH084053 / MH / NIMH NIH HHS / United States
P50 CA097007 / CA / NCI NIH HHS / United States
R37 MH057881 / MH / NIMH NIH HHS / United States
HHSN271201300031C / MH / NIMH NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
R01 MH080405 / MH / NIMH NIH HHS / United States
R01 CA133996 / CA / NCI NIH HHS / United States
098051 / / Wellcome Trust / United Kingdom
P50 CA093459 / CA / NCI NIH HHS / United States
R01 ES011740 / ES / NIEHS NIH HHS / United States
R01 MH075916 / MH / NIMH NIH HHS / United States
K01 MH109782 / MH / NIMH NIH HHS / United States
R01 MH093725 / MH / NIMH NIH HHS / United States
P50 MH066392 / MH / NIMH NIH HHS / United States
R01 MH085542 / MH / NIMH NIH HHS / United States