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; G Breen; Eating Disorder Working Group of the Psychiatric Genomics Consortium

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 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, G Breen, Eating Disorder Working Group of the Psychiatric Genomics Consortium

Section of Eating Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Klinik für Kinder- und Jugendpsychiatrie, Psychotherapie und Psychosomatik Klinikum Frankfurt, Frankfurt, Germany.
TU Dresden
Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University Hospital Essen and University of Duisburg-Essen, Essen, Germany.
Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.
Division of Psychological &Social Medicine and Developmental Neurosciences, Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, Dresden, Germany.
Erasmus University Medical Center
Massachusetts General Hospital
University of Helsinki
UMC University Medical Center Utrecht
INSERM U984, Centre of Psychiatry and Neuroscience, Paris, France.
Mary Sue Coleman Director, Life Sciences Institute, Professor of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
Rivierduinen Eating Disorders Ursula, Leiden, Zuid-Holland, The Netherlands.
Eating Disorders Unit, 1st Department of Psychiatry, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Harvard Medical School
University of Groningen
University of Aberdeen
Norwegian Institute of Public Health
University of Campania Luigi Vanvitelli
University of Salerno
University of Cyprus
King's College London
Wellcome Sanger Institute
University of North Carolina at Chapel Hill

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

36 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.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.

Original language	English
Pages (from-to)	1169–1180
Journal	Molecular Psychiatry
Volume	23
Issue number	5
Early online date	25 Jul 2017
DOIs	https://doi.org/10.1038/mp.2017.88
Publication status	Published - 2018

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Journal Article

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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., ... 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

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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.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.",

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pages = "1169–1180",

journal = "Molecular Psychiatry",

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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, G-P, Slof-Op 't Landt, MCT, Maj, M, Monteleone, AM, Monteleone, P, Raevuori, AH, Reichborn-Kjennerud, T, Tozzi, F, Breen, G & 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

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 - Breen, G

AU - Eating Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2018

Y1 - 2018

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.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.

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.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.

KW - Journal Article

UR - https://www.scopus.com/pages/publications/85029816710

U2 - 10.1038/mp.2017.88

DO - 10.1038/mp.2017.88

M3 - Article

C2 - 29155802

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

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