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; F. Aguilera-Mckay; J. Treasure; U. Schmidt; C. Gunasinghe; A. Romero; C. Curtis; D. Rhodes; J. Moens; G. Kalsi; D. Dempster; R. Leung; A. Keohane; R. Burghardt; S. Ehrlich; J. Hebebrand; A. Hinney; A. Ludolph; E. Walton; P. Deloukas; A. Hofman; A. Palotie; P. Palta; F. J.A. van Rooij; K. Stirrups; R. Adan; C. Boni; R. Cone; G. Dedoussis; E. van Furth; F. Gonidakis; P. Gorwood; J. Hudson; J. Kaprio; M. Kas; A. Keski-Rahonen; K. Kiezebrink; G. P. Knudsen; M. C.T. Slof-Op ’T Landt; M. Maj; A. M. Monteleone; P. Monteleone; A. H. Raevuori; T. Reichborn-Kjennerud; F. Tozzi; A. Tsitsika; A. Elburg; D. A. Collier; P. F. Sullivan; G. Breen; C. M. Bulik; E. Zeggini; R. A.H. Adan; L. Alfredsson; T. Ando; O. A. Andreassen; H. Aschauer; J. H. Baker; J. C. Barrett; V. Bencko; A. W. Bergen; W. H. Berrettini; A. Birgegård; C. Boni; V. Boraska Perica; H. Brandt; C. M. Bulik; L. Carlberg; M. Cassina; S. Cichon; M. Clementi; S. Cohen-Woods; J. Coleman; R. D. Cone; P. Courtet; S. Crawford; S. Crow; J. Crowley; U. N. Danner; O. S.P. Davis; M. Zwaan; G. Dedoussis; D. Degortes; J. E. Desocio; D. M. Dick; D. Dikeos; C. Dina; B. Ding; M. Dmitrzak-Weglarz; E. Docampo; L. Duncan; K. Egberts; G. Escaramís; T. Esko; T. Espeseth; X. Estivill; A. Favaro; F. Fernández-Aranda; M. M. Fichter; C. Finan; K. Fischer; J. A.B. Floyd; L. Foretova; M. Forzan; C. S. Franklin; S. Gallinger; G. Gambaro; H. A. Gaspar; I. Giegling; F. Gonidakis; P. Gorwood; M. Gratacos; S. Guillaume; Y. Guo; H. Hakonarson; K. A. Halmi; K. Hatzikotoulas; J. Hauser; J. Hebebrand; S. Helder; S. Herms; B. Herpertz-Dahlmann; W. Herzog; C. E. Hilliard; C. Hübel; L. M. Huckins; J. I. Hudson; J. Huemer; H. Inoko; V. Janout; S. Jiménez-Murcia; C. Johnson; A. Julià; A. Juréus; G. Kalsi; D. Kaminska; A. S. Kaplan; L. Karhunen; A. Karwautz; M. J.H. Kas; W. Kaye; J. L. Kennedy; A. Keski-Rahkonen; K. Kiezebrink; L. Klareskog; K. L. Klump; G. P.S. Knudsen; B. P.C. Koeleman; D. Koubek; MC C.L. Via; M. Landén; S. Le Hellard; R. D. Levitan; D. Li; P. Lichtenstein; L. Lilenfeld; J. Lissowska; A. Lundervold; P. Magistretti; K. Mannik; S. Marsal; N. Martin; M. Mattingsdal; S. McDevitt; P. McGuffin; E. Merl; A. Metspalu; I. Meulenbelt; N. Micali; J. Mitchell; K. Mitchell; P. Mortensen; M. A. Munn-Chernoff; M. Navratilova; I. Nilsson; C. Norring; I. Ntalla; R. A. Ophoff; J. K. O'toole; J. Pantel; H. Papezova; D. Pinto; R. Rabionet; A. Raevuori; A. Rajewski; N. Ramoz; N. W. Rayner; T. Reichborn-Kjennerud; S. Ripatti; M. Roberts; A. Rotondo; D. Rujescu; F. Rybakowski; P. Santonastaso; A. Scherag; S. W. Scherer; U. Schmidt; N. J. Schork; A. Schosser; L. Slachtova; R. Sladek; P. E. Slagboom; A. Slopien; N. Soranzo; L. Southam; V. M. Steen; E. Strengman; M. Strober; J. P. Szatkiewicz; N. Szeszenia-Dabrowska; I. Tachmazidou; E. Tenconi; L. M. Thornton; A. Tortorella; F. Tozzi; K. Tziouvas; A. A. Elburg; E. F. Furth; G. Wagner; E. Walton; H. Watson; H. E. Wichmann; E. Widen; D. B. Woodside; J. Yanovski; S. Yao; Z. Yilmaz; E. Zeggini; S. Zerwas; S. Zipfel

doi:10.1038/mp.2017.88

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, F. Aguilera-Mckay, J. Treasure, U. Schmidt, C. Gunasinghe, A. Romero, C. Curtis, D. Rhodes, J. Moens, G. Kalsi, D. Dempster, R. Leung, A. Keohane, R. Burghardt, S. Ehrlich, J. HebebrandA. Hinney, A. Ludolph, E. Walton, P. Deloukas, A. Hofman, A. Palotie, P. Palta, F. J.A. van Rooij, K. Stirrups, R. Adan, C. Boni, R. Cone, G. Dedoussis, E. van Furth, F. Gonidakis, P. Gorwood, J. Hudson, J. Kaprio, M. Kas, A. Keski-Rahonen, K. Kiezebrink, G. P. Knudsen, M. C.T. Slof-Op ’T Landt, M. Maj, A. M. Monteleone, P. Monteleone, A. H. Raevuori, T. Reichborn-Kjennerud, F. Tozzi, A. Tsitsika, A. Elburg, D. A. Collier, P. F. Sullivan, G. Breen, C. M. Bulik, E. Zeggini, R. A.H. Adan, L. Alfredsson, T. Ando, O. A. Andreassen, H. Aschauer, J. H. Baker, J. C. Barrett, V. Bencko, A. W. Bergen, W. H. Berrettini, A. Birgegård, C. Boni, V. Boraska Perica, H. Brandt, C. M. Bulik, L. Carlberg, M. Cassina, S. Cichon, M. Clementi, S. Cohen-Woods, J. Coleman, R. D. Cone, P. Courtet, S. Crawford, S. Crow, J. Crowley, U. N. Danner, O. S.P. Davis, M. Zwaan, G. Dedoussis, D. Degortes, J. E. Desocio, D. M. Dick, D. Dikeos, C. Dina, B. Ding, M. Dmitrzak-Weglarz, E. Docampo, L. Duncan, K. Egberts, G. Escaramís, T. Esko, T. Espeseth, X. Estivill, A. Favaro, F. Fernández-Aranda, M. M. Fichter, C. Finan, K. Fischer, J. A.B. Floyd, L. Foretova, M. Forzan, C. S. Franklin, S. Gallinger, G. Gambaro, H. A. Gaspar, I. Giegling, F. Gonidakis, P. Gorwood, M. Gratacos, S. Guillaume, Y. Guo, H. Hakonarson, K. A. Halmi, K. Hatzikotoulas, J. Hauser, J. Hebebrand, S. Helder, S. Herms, B. Herpertz-Dahlmann, W. Herzog, C. E. Hilliard, C. Hübel, L. M. Huckins, J. I. Hudson, J. Huemer, H. Inoko, V. Janout, S. Jiménez-Murcia, C. Johnson, A. Julià, A. Juréus, G. Kalsi, D. Kaminska, A. S. Kaplan, L. Karhunen, A. Karwautz, M. J.H. Kas, W. Kaye, J. L. Kennedy, A. Keski-Rahkonen, K. Kiezebrink, L. Klareskog, K. L. Klump, G. P.S. Knudsen, B. P.C. Koeleman, D. Koubek, MC C.L. Via, M. Landén, S. Le Hellard, R. D. Levitan, D. Li, P. Lichtenstein, L. Lilenfeld, J. Lissowska, A. Lundervold, P. Magistretti, K. Mannik, S. Marsal, N. Martin, M. Mattingsdal, S. McDevitt, P. McGuffin, E. Merl, A. Metspalu, I. Meulenbelt, N. Micali, J. Mitchell, K. Mitchell, P. Mortensen, M. A. Munn-Chernoff, M. Navratilova, I. Nilsson, C. Norring, I. Ntalla, R. A. Ophoff, J. K. O'toole, J. Pantel, H. Papezova, D. Pinto, R. Rabionet, A. Raevuori, A. Rajewski, N. Ramoz, N. W. Rayner, T. Reichborn-Kjennerud, S. Ripatti, M. Roberts, A. Rotondo, D. Rujescu, F. Rybakowski, P. Santonastaso, A. Scherag, S. W. Scherer, U. Schmidt, N. J. Schork, A. Schosser, L. Slachtova, R. Sladek, P. E. Slagboom, A. Slopien, N. Soranzo, L. Southam, V. M. Steen, E. Strengman, M. Strober, J. P. Szatkiewicz, N. Szeszenia-Dabrowska, I. Tachmazidou, E. Tenconi, L. M. Thornton, A. Tortorella, F. Tozzi, K. Tziouvas, A. A. Elburg, E. F. Furth, G. Wagner, E. Walton, H. Watson, H. E. Wichmann, E. Widen, D. B. Woodside, J. Yanovski, S. Yao, Z. Yilmaz, E. Zeggini, S. Zerwas, S. Zipfel

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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 language	English
Pages (from-to)	1169-1180
Number of pages	12
Journal	Molecular Psychiatry
Volume	23
Issue number	5
DOIs	https://doi.org/10.1038/mp.2017.88
State	Published - 1 May 2018

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10.1038/mp.2017.88

Cite this

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., ... Zipfel, S. (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

@article{396655bdd02b4be39a1cee0785834f92,

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

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.",

author = "Huckins, {L. M.} and K. Hatzikotoulas and L. Southam and Thornton, {L. M.} and J. Steinberg and F. Aguilera-Mckay and J. Treasure and U. Schmidt and C. Gunasinghe and A. Romero and C. Curtis and D. Rhodes and J. Moens and G. Kalsi and D. Dempster and R. Leung and A. Keohane and R. Burghardt and S. Ehrlich and J. Hebebrand and A. Hinney and A. Ludolph and E. Walton and P. Deloukas and A. Hofman and A. Palotie and P. Palta and {van Rooij}, {F. J.A.} and K. Stirrups and R. Adan and C. Boni and R. Cone and G. Dedoussis and {van Furth}, E. and F. Gonidakis and P. Gorwood and J. Hudson and J. Kaprio and M. Kas and A. Keski-Rahonen and K. Kiezebrink and Knudsen, {G. P.} and {Slof-Op {\textquoteright}T Landt}, {M. C.T.} and M. Maj and Monteleone, {A. M.} and P. Monteleone and Raevuori, {A. H.} and T. Reichborn-Kjennerud and F. Tozzi and A. Tsitsika and A. Elburg and Collier, {D. A.} and Sullivan, {P. F.} and G. Breen and Bulik, {C. M.} and E. Zeggini and Adan, {R. A.H.} and L. Alfredsson and T. Ando and Andreassen, {O. A.} and H. Aschauer and Baker, {J. H.} and Barrett, {J. C.} and V. Bencko and Bergen, {A. W.} and Berrettini, {W. H.} and A. Birgeg{\aa}rd and C. Boni and Perica, {V. Boraska} and H. Brandt and Bulik, {C. M.} and L. Carlberg and M. Cassina and S. Cichon and M. Clementi and S. Cohen-Woods and J. Coleman and Cone, {R. D.} and P. Courtet and S. Crawford and S. Crow and J. Crowley and Danner, {U. N.} and Davis, {O. S.P.} and M. Zwaan and G. Dedoussis and D. Degortes and Desocio, {J. E.} and Dick, {D. M.} and D. Dikeos and C. Dina and B. Ding and M. Dmitrzak-Weglarz and E. Docampo and L. Duncan and K. Egberts and G. Escaram{\'i}s and T. Esko and T. Espeseth and X. Estivill and A. Favaro and F. Fern{\'a}ndez-Aranda and Fichter, {M. M.} and C. Finan and K. Fischer and Floyd, {J. A.B.} and L. Foretova and M. Forzan and Franklin, {C. S.} and S. Gallinger and G. Gambaro and Gaspar, {H. A.} and I. Giegling and F. Gonidakis and P. Gorwood and M. Gratacos and S. Guillaume and Y. Guo and H. Hakonarson and Halmi, {K. A.} and K. Hatzikotoulas and J. Hauser and J. Hebebrand and S. Helder and S. Herms and B. Herpertz-Dahlmann and W. Herzog and Hilliard, {C. E.} and C. H{\"u}bel and Huckins, {L. M.} and Hudson, {J. I.} and J. Huemer and H. Inoko and V. Janout and S. Jim{\'e}nez-Murcia and C. Johnson and A. Juli{\`a} and A. Jur{\'e}us and G. Kalsi and D. Kaminska and Kaplan, {A. S.} and L. Karhunen and A. Karwautz and Kas, {M. J.H.} and W. Kaye and Kennedy, {J. L.} and A. Keski-Rahkonen and K. Kiezebrink and L. Klareskog and Klump, {K. L.} and Knudsen, {G. P.S.} and Koeleman, {B. P.C.} and D. Koubek and Via, {MC C.L.} and M. Land{\'e}n and Hellard, {S. Le} and Levitan, {R. D.} and D. Li and P. Lichtenstein and L. Lilenfeld and J. Lissowska and A. Lundervold and P. Magistretti and K. Mannik and S. Marsal and N. Martin and M. Mattingsdal and S. McDevitt and P. McGuffin and E. Merl and A. Metspalu and I. Meulenbelt and N. Micali and J. Mitchell and K. Mitchell and P. Mortensen and Munn-Chernoff, {M. A.} and M. Navratilova and I. Nilsson and C. Norring and I. Ntalla and Ophoff, {R. A.} and O'toole, {J. K.} and J. Pantel and H. Papezova and D. Pinto and R. Rabionet and A. Raevuori and A. Rajewski and N. Ramoz and Rayner, {N. W.} and T. Reichborn-Kjennerud and S. Ripatti and M. Roberts and A. Rotondo and D. Rujescu and F. Rybakowski and P. Santonastaso and A. Scherag and Scherer, {S. W.} and U. Schmidt and Schork, {N. J.} and A. Schosser and L. Slachtova and R. Sladek and Slagboom, {P. E.} and A. Slopien and N. Soranzo and L. Southam and Steen, {V. M.} and E. Strengman and M. Strober and Szatkiewicz, {J. P.} and N. Szeszenia-Dabrowska and I. Tachmazidou and E. Tenconi and Thornton, {L. M.} and A. Tortorella and F. Tozzi and K. Tziouvas and Elburg, {A. A.} and Furth, {E. F.} and G. Wagner and E. Walton and H. Watson and Wichmann, {H. E.} and E. Widen and Woodside, {D. B.} and J. Yanovski and S. Yao and Z. Yilmaz and E. Zeggini and S. Zerwas and S. Zipfel",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2018.",

year = "2018",

month = may,

day = "1",

doi = "10.1038/mp.2017.88",

language = "English",

volume = "23",

pages = "1169--1180",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

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Huckins, 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, GP, Slof-Op ’T Landt, MCT, Maj, M, Monteleone, AM, Monteleone, P, Raevuori, AH, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, Elburg, A, Collier, DA, Sullivan, PF, Breen, G, Bulik, CM, Zeggini, E, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Aschauer, H, Baker, JH, Barrett, JC, Bencko, V, Bergen, AW, Berrettini, WH, Birgegård, A, Boni, C, Perica, VB, Brandt, H, Bulik, CM, Carlberg, L, Cassina, M, Cichon, S, Clementi, M, Cohen-Woods, S, Coleman, J, Cone, RD, Courtet, P, Crawford, S, Crow, S, Crowley, J, Danner, UN, Davis, OSP, Zwaan, M, Dedoussis, G, Degortes, D, Desocio, JE, Dick, DM, Dikeos, D, Dina, C, Ding, B, Dmitrzak-Weglarz, M, Docampo, E, Duncan, L, Egberts, K, Escaramís, G, Esko, T, Espeseth, T, Estivill, X, Favaro, A, Fernández-Aranda, F, Fichter, MM, Finan, C, Fischer, K, Floyd, JAB, Foretova, L, Forzan, M, Franklin, CS, Gallinger, S, Gambaro, G, Gaspar, HA, Giegling, I, Gonidakis, F, Gorwood, P, Gratacos, M, Guillaume, S, Guo, Y, Hakonarson, H, Halmi, KA, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, S, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Hilliard, CE, Hübel, C, Huckins, LM, Hudson, JI, Huemer, J, Inoko, H, Janout, V, Jiménez-Murcia, S, Johnson, C, Julià, A, Juréus, A, Kalsi, G, Kaminska, D, Kaplan, AS, Karhunen, L, Karwautz, A, Kas, MJH, Kaye, W, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Klareskog, L, Klump, KL, Knudsen, GPS, Koeleman, BPC, Koubek, D, Via, MCCL, Landén, M, Hellard, SL, Levitan, RD, Li, D, Lichtenstein, P, Lilenfeld, L, Lissowska, J, Lundervold, A, Magistretti, P, Mannik, K, Marsal, S, Martin, N, Mattingsdal, M, McDevitt, S, McGuffin, P, Merl, E, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, J, Mitchell, K, Mortensen, P, Munn-Chernoff, MA, Navratilova, M, Nilsson, I, Norring, C, Ntalla, I, Ophoff, RA, O'toole, JK, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Rajewski, A, Ramoz, N, Rayner, NW, Reichborn-Kjennerud, T, Ripatti, S, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Slachtova, L, Sladek, R, Slagboom, PE, Slopien, A, Soranzo, N, Southam, L, Steen, VM, Strengman, E, Strober, M, Szatkiewicz, JP, Szeszenia-Dabrowska, N, Tachmazidou, I, Tenconi, E, Thornton, LM, Tortorella, A, Tozzi, F, Tziouvas, K, Elburg, AA, Furth, EF, Wagner, G, Walton, E, Watson, H, Wichmann, HE, Widen, E, Woodside, DB, Yanovski, J, Yao, S, Yilmaz, Z, Zeggini, E, Zerwas, S & Zipfel, S 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

TY - JOUR

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

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 - 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 - 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.

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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

C2 - 29155802

AN - SCOPUS:85029816710

SN - 1359-4184

VL - 23

SP - 1169

EP - 1180

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 5

ER -

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

Abstract

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