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

Eating Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

3 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

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Anorexia Nervosa
Genome-Wide Association Study
Genome
Exome
Computer Simulation
Fear
Body Weight
Weights and Measures
Population

Cite this

Eating Disorder Working Group of the Psychiatric Genomics Consortium (2018). Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry, 23(5), 1169-1180. https://doi.org/10.1038/mp.2017.88
Eating Disorder Working Group of the Psychiatric Genomics Consortium. / Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. In: Molecular Psychiatry. 2018 ; Vol. 23, No. 5. pp. 1169-1180.
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Eating Disorder Working Group of the Psychiatric Genomics Consortium 2018, 'Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa' Molecular Psychiatry, vol. 23, no. 5, pp. 1169-1180. https://doi.org/10.1038/mp.2017.88

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. / Eating Disorder Working Group of the Psychiatric Genomics Consortium.

In: Molecular Psychiatry, Vol. 23, No. 5, 01.05.2018, p. 1169-1180.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

AU - Eating Disorder Working Group of the Psychiatric Genomics Consortium

AU - Huckins, L. M.

AU - Hatzikotoulas, K.

AU - Southam, L.

AU - Thornton, L. M.

AU - Steinberg, J.

AU - Aguilera-Mckay, F.

AU - Treasure, J.

AU - Schmidt, U.

AU - Gunasinghe, C.

AU - Romero, A.

AU - Curtis, C.

AU - Rhodes, D.

AU - Moens, J.

AU - Kalsi, G.

AU - Dempster, D.

AU - Leung, R.

AU - Keohane, A.

AU - Burghardt, R.

AU - Ehrlich, S.

AU - Hebebrand, J.

AU - Hinney, A.

AU - Ludolph, A.

AU - Walton, E.

AU - Deloukas, P.

AU - Hofman, A.

AU - Palotie, A.

AU - Palta, P.

AU - van Rooij, F. J.A.

AU - Stirrups, K.

AU - Adan, R.

AU - Boni, C.

AU - Cone, R.

AU - Dedoussis, G.

AU - van Furth, E.

AU - Gonidakis, F.

AU - Gorwood, P.

AU - Hudson, J.

AU - Kaprio, J.

AU - Kas, M.

AU - Keski-Rahonen, A.

AU - Kiezebrink, K.

AU - Knudsen, G. P.

AU - Slof-Op ’T Landt, M. C.T.

AU - Maj, M.

AU - Monteleone, A. M.

AU - Monteleone, P.

AU - Raevuori, A. H.

AU - Reichborn-Kjennerud, T.

AU - Tozzi, F.

AU - Tsitsika, A.

AU - Elburg, A.

AU - Collier, D. A.

AU - Sullivan, P. F.

AU - Breen, G.

AU - Bulik, C. M.

AU - Zeggini, E.

AU - Adan, R. A.H.

AU - Alfredsson, L.

AU - Ando, T.

AU - Andreassen, O. A.

AU - Aschauer, H.

AU - Baker, J. H.

AU - Barrett, J. C.

AU - Bencko, V.

AU - Bergen, A. W.

AU - Berrettini, W. H.

AU - Birgegård, A.

AU - Boni, C.

AU - Perica, V. Boraska

AU - Brandt, H.

AU - Breen, G.

AU - Bulik, C. M.

AU - Carlberg, L.

AU - Cassina, M.

AU - Cichon, S.

AU - Clementi, M.

AU - Cohen-Woods, S.

AU - Coleman, J.

AU - Cone, R. D.

AU - Courtet, P.

AU - Crawford, S.

AU - Crow, S.

AU - Crowley, J.

AU - Danner, U. N.

AU - Davis, O. S.P.

AU - Zwaan, M.

AU - Dedoussis, G.

AU - Degortes, D.

AU - Desocio, J. E.

AU - Dick, D. M.

AU - Dikeos, D.

AU - Dina, C.

AU - Ding, B.

AU - Dmitrzak-Weglarz, M.

AU - Docampo, E.

AU - Duncan, L.

AU - Egberts, K.

AU - Ehrlich, S.

AU - Escaramís, G.

AU - Esko, T.

AU - Espeseth, T.

AU - Estivill, X.

AU - Favaro, A.

AU - Fernández-Aranda, F.

AU - Fichter, M. M.

AU - Finan, C.

AU - Fischer, K.

AU - Floyd, J. A.B.

AU - Foretova, L.

AU - Forzan, M.

AU - Franklin, C. S.

AU - Gallinger, S.

AU - Gambaro, G.

AU - Gaspar, H. A.

AU - Giegling, I.

AU - Gonidakis, F.

AU - Gorwood, P.

AU - Gratacos, M.

AU - Guillaume, S.

AU - Guo, Y.

AU - Hakonarson, H.

AU - Halmi, K. A.

AU - Hatzikotoulas, K.

AU - Hauser, J.

AU - Hebebrand, J.

AU - Helder, S.

AU - Herms, S.

AU - Herpertz-Dahlmann, B.

AU - Herzog, W.

AU - Hilliard, C. E.

AU - Hinney, A.

AU - Hübel, C.

AU - Huckins, L. M.

AU - Hudson, J. I.

AU - Huemer, J.

AU - Inoko, H.

AU - Janout, V.

AU - Jiménez-Murcia, S.

AU - Johnson, C.

AU - Julià, A.

AU - Juréus, A.

AU - Kalsi, G.

AU - Kaminska, D.

AU - Kaplan, A. S.

AU - Kaprio, J.

AU - Karhunen, L.

AU - Karwautz, A.

AU - Kas, M. J.H.

AU - Kaye, W.

AU - Kennedy, J. L.

AU - Keski-Rahkonen, A.

AU - Kiezebrink, K.

AU - Klareskog, L.

AU - Klump, K. L.

AU - Knudsen, G. P.S.

AU - Koeleman, B. P.C.

AU - Koubek, D.

AU - Via, MC C.L.

AU - Landén, M.

AU - Hellard, S. Le

AU - Levitan, R. D.

AU - Li, D.

AU - Lichtenstein, P.

AU - Lilenfeld, L.

AU - Lissowska, J.

AU - Lundervold, A.

AU - Magistretti, P.

AU - Maj, M.

AU - Mannik, K.

AU - Marsal, S.

AU - Martin, N.

AU - Mattingsdal, M.

AU - McDevitt, S.

AU - McGuffin, P.

AU - Merl, E.

AU - Metspalu, A.

AU - Meulenbelt, I.

AU - Micali, N.

AU - Mitchell, J.

AU - Mitchell, K.

AU - Monteleone, P.

AU - Monteleone, A. M.

AU - Mortensen, P.

AU - Munn-Chernoff, M. A.

AU - Navratilova, M.

AU - Nilsson, I.

AU - Norring, C.

AU - Ntalla, I.

AU - Ophoff, R. A.

AU - O'toole, J. K.

AU - Palotie, A.

AU - Pantel, J.

AU - Papezova, H.

AU - Pinto, D.

AU - Rabionet, R.

AU - Raevuori, A.

AU - Rajewski, A.

AU - Ramoz, N.

AU - Rayner, N. W.

AU - Reichborn-Kjennerud, T.

AU - Ripatti, S.

AU - Roberts, M.

AU - Rotondo, A.

AU - Rujescu, D.

AU - Rybakowski, F.

AU - Santonastaso, P.

AU - Scherag, A.

AU - Scherer, S. W.

AU - Schmidt, U.

AU - Schork, N. J.

AU - Schosser, A.

AU - Slachtova, L.

AU - Sladek, R.

AU - Slagboom, P. E.

AU - Slof-Op 'T Landt, M. C.T.

AU - Slopien, A.

AU - Soranzo, N.

AU - Southam, L.

AU - Steen, V. M.

AU - Strengman, E.

AU - Strober, M.

AU - Sullivan, P. F.

AU - Szatkiewicz, J. P.

AU - Szeszenia-Dabrowska, N.

AU - Tachmazidou, I.

AU - Tenconi, E.

AU - Thornton, L. M.

AU - Tortorella, A.

AU - Tozzi, F.

AU - Treasure, J.

AU - Tsitsika, A.

AU - Tziouvas, K.

AU - Elburg, A. A.

AU - Furth, E. F.

AU - Wagner, G.

AU - Walton, E.

AU - Watson, H.

AU - Wichmann, H. E.

AU - Widen, E.

AU - Woodside, D. B.

AU - Yanovski, J.

AU - Yao, S.

AU - Yilmaz, Z.

AU - Zeggini, E.

AU - Zerwas, S.

AU - Zipfel, S.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029816710&partnerID=8YFLogxK

U2 - 10.1038/mp.2017.88

DO - 10.1038/mp.2017.88

M3 - Article

VL - 23

SP - 1169

EP - 1180

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 5

ER -

Eating Disorder Working Group of the Psychiatric Genomics Consortium. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry. 2018 May 1;23(5):1169-1180. https://doi.org/10.1038/mp.2017.88