A genome-wide association study of anorexia nervosa

V Boraska; C Franklin; J Floyd; M Thornton; L Huckins; L Southam; N Rayner; I Tachmazidou; K Klump; J Treasure; C Lewis; U Schmidt; F Tozzi; K Kiezebrink; J Hebebrand; P Gorwood; H Adan; M Kas; A Favaro; P Santonastaso; F Fernández-Aranda; M Gratacos; F Rybakowski; M Dmitrzak-Weglarz; J Kaprio; A Keski-Rahkonen; A Raevuori; E Van Furth; Margarita Landt; James Hudson; Ted Reichborn-Kjennerud; Gun Knudsen; Palmiero Monteleone; Allan Kaplan; Adnreas Karwautz; Hakon Hakonarson; Wade Berrettini; Yiran Guo; Dong Li; Nicholas Schork; Gen Komaki; Tetsuya Ando; Hidetoshi Inoko; Tõnu Esko; Krista Fischer; Katrin Mannik; Andres Metspalu; Jessica Baker; Roger Cone; Jennifer Dackor; Janeice DeSocio; Christopher Hilliard; Julie O'Toole; Jaques Pantel; Jin Szatkiewicz; Chrysecollo Taico; Stephanie Zerwas; Sara Trace; Oliver Davis; Sietske Helder; Katharina Buhren; Roland Burghardt; Martina de Zwaan; Karin Egbert; Stefan Ehrlich; Beate Herpetz-Dahlmann; Wolfgang Herzog; Hartmut Imgart; Andre Scherag; Susann Scherag; Stephan Zipfell; Claudette Boni; Nicolas Ramoz; Audrey Versini; Marek Brandys; Unna Danner; Carlien de Koval; Judith Hendricks; Bobby Koeleman; Roel Ophoff; Eric Strengman; Annemarie van Elburg; Alice Bruson; Maurizio Clementi; Daniela Degortes; Monica Forzan; Elena Tenconi; Elisa Docampo; Georgia Escaramis; Susana Jimenez-Murcia; Jolanta Lissowska; Andrzej Rajewski; Neonila Szeszenia-Dabrowska; Agnieszka Slopien; Joanna Hauser; Lelia Karhunen; Ingrid Meulenbelt; Eline Slagboom; Alfonso Tortorella; Mario Maj; George Dedoussis; Dimitris Dikeos; Fragiskos Gonidakis; Konstantinos Tziouvas; Artemis Tsitsika; Hana Papezova; Lenka Slachtova; Debora Martaskova; James Kennedy; Robert Levitan; Zeynep Yilmaz; Julia Heumer; Doris Koubek; Elisabeth Merl; Gudrun Wagner; Paul Lichtenstein; Gerome Breen; Sarah Cohen-Woods; Anne Farmer; Peter McGuffin; Sven Cichon; Ina Giegling; Stefan Herms; Dan Rujescu; Stefan Schreiber; H. Erich Wichmann; Christian Dina; Rob Sladek; Giovanni Gambaro; Nicole Soranzo; Antonio Julia; Sara Marsal; Raquel Rabionet; Valerie Gaborieau; Danielle Dick; Aarno Palotie; Samuli Ripatti; Elisabeth Widen; Ole Andreassen; Thomas Espeseth; Astri Lundervold; Ivar Reinvang; Vidar Steen; Stephanie Le Hellard; Morten Mattingsdal; Ionna Ntalla; Vladimir Bencko; Lenka Faretova; Vladimir Janout; Marie Navratilova; Steven Gallinger; Dalila Pinto; Stephen Scherer; Harald Aschauer; Laura Carlberg; Alexandra Schosser; Lars Alfredsson; Bo Ding; Lars Klareskog; Leonid Padyukov; Chris Finan; Gursharan Kalsi; Marion Roberts; Darren Logan; Leena Peltonen; Graham Ritchie; Jeffrey Barrett; Xavier Estivill; Anke Hinney; Patrick Sullivan; David Collier; Eleftheria Zeggini; Cynthia Bulik

doi:10.1038/mp.2013.187

A genome-wide association study of anorexia nervosa

V Boraska, C Franklin, J Floyd, M Thornton, L Huckins, L Southam, N Rayner, I Tachmazidou, K Klump, J Treasure, C Lewis, U Schmidt, F Tozzi, K Kiezebrink, J Hebebrand, P Gorwood, H Adan, M Kas, A Favaro, P SantonastasoF Fernández-Aranda, M Gratacos, F Rybakowski, M Dmitrzak-Weglarz, J Kaprio, A Keski-Rahkonen, A Raevuori, E Van Furth, Margarita Landt, James Hudson, Ted Reichborn-Kjennerud, Gun Knudsen, Palmiero Monteleone, Allan Kaplan, Adnreas Karwautz, Hakon Hakonarson, Wade Berrettini, Yiran Guo, Dong Li, Nicholas Schork, Gen Komaki, Tetsuya Ando, Hidetoshi Inoko, Tõnu Esko, Krista Fischer, Katrin Mannik, Andres Metspalu, Jessica Baker, Roger Cone, Jennifer Dackor, Janeice DeSocio, Christopher Hilliard, Julie O'Toole, Jaques Pantel, Jin Szatkiewicz, Chrysecollo Taico, Stephanie Zerwas, Sara Trace, Oliver Davis, Sietske Helder, Katharina Buhren, Roland Burghardt, Martina de Zwaan, Karin Egbert, Stefan Ehrlich, Beate Herpetz-Dahlmann, Wolfgang Herzog, Hartmut Imgart, Andre Scherag, Susann Scherag, Stephan Zipfell, Claudette Boni, Nicolas Ramoz, Audrey Versini, Marek Brandys, Unna Danner, Carlien de Koval, Judith Hendricks, Bobby Koeleman, Roel Ophoff, Eric Strengman, Annemarie van Elburg, Alice Bruson, Maurizio Clementi, Daniela Degortes, Monica Forzan, Elena Tenconi, Elisa Docampo, Georgia Escaramis, Susana Jimenez-Murcia, Jolanta Lissowska, Andrzej Rajewski, Neonila Szeszenia-Dabrowska, Agnieszka Slopien, Joanna Hauser, Lelia Karhunen, Ingrid Meulenbelt, Eline Slagboom, Alfonso Tortorella, Mario Maj, George Dedoussis, Dimitris Dikeos, Fragiskos Gonidakis, Konstantinos Tziouvas, Artemis Tsitsika, Hana Papezova, Lenka Slachtova, Debora Martaskova, James Kennedy, Robert Levitan, Zeynep Yilmaz, Julia Heumer, Doris Koubek, Elisabeth Merl, Gudrun Wagner, Paul Lichtenstein, Gerome Breen, Sarah Cohen-Woods, Anne Farmer, Peter McGuffin, Sven Cichon, Ina Giegling, Stefan Herms, Dan Rujescu, Stefan Schreiber, H. Erich Wichmann, Christian Dina, Rob Sladek, Giovanni Gambaro, Nicole Soranzo, Antonio Julia, Sara Marsal, Raquel Rabionet, Valerie Gaborieau, Danielle Dick, Aarno Palotie, Samuli Ripatti, Elisabeth Widen, Ole Andreassen, Thomas Espeseth, Astri Lundervold, Ivar Reinvang, Vidar Steen, Stephanie Le Hellard, Morten Mattingsdal, Ionna Ntalla, Vladimir Bencko, Lenka Faretova, Vladimir Janout, Marie Navratilova, Steven Gallinger, Dalila Pinto, Stephen Scherer, Harald Aschauer, Laura Carlberg, Alexandra Schosser, Lars Alfredsson, Bo Ding, Lars Klareskog, Leonid Padyukov, Chris Finan, Gursharan Kalsi, Marion Roberts, Darren Logan, Leena Peltonen, Graham Ritchie, Jeffrey Barrett, Xavier Estivill, Anke Hinney, Patrick Sullivan, David Collier, Eleftheria Zeggini, Cynthia Bulik

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

209 Citations (Scopus)

Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 × 10^-7) in SOX2OT and rs17030795 (P = 5.84 × 10^-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 × 10^-6) between CUL3 and FAM124B and rs1886797 (P = 8.05 × 10^-6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4 × 10^-6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Original language	English
Pages (from-to)	1085-1094
Number of pages	10
Journal	MOLECULAR PSYCHIATRY
Volume	19
Issue number	10
DOIs	https://doi.org/10.1038/mp.2013.187
Publication status	Published - 1 Oct 2014

Keywords

Anorexia nervosa
Body mass index
Eating disorders
Genome-wide association study
GWAS
Metabolic

Access to Document

10.1038/mp.2013.187

Cite this

Boraska, V., Franklin, C., Floyd, J., Thornton, M., Huckins, L., Southam, L., Rayner, N., Tachmazidou, I., Klump, K., Treasure, J., Lewis, C., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, H., Kas, M., Favaro, A., ... Bulik, C. (2014). A genome-wide association study of anorexia nervosa. MOLECULAR PSYCHIATRY, 19(10), 1085-1094. https://doi.org/10.1038/mp.2013.187

@article{c6f9663395ac49dabf1ec084ec4819b9,

title = "A genome-wide association study of anorexia nervosa",

abstract = "Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 × 10-7) in SOX2OT and rs17030795 (P = 5.84 × 10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 × 10-6) between CUL3 and FAM124B and rs1886797 (P = 8.05 × 10-6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4 × 10-6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.",

keywords = "Anorexia nervosa, Body mass index, Eating disorders, Genome-wide association study, GWAS, Metabolic",

author = "V Boraska and C Franklin and J Floyd and M Thornton and L Huckins and L Southam and N Rayner and I Tachmazidou and K Klump and J Treasure and C Lewis and U Schmidt and F Tozzi and K Kiezebrink and J Hebebrand and P Gorwood and H Adan and M Kas and A Favaro and P Santonastaso and F Fern{\'a}ndez-Aranda and M Gratacos and F Rybakowski and M Dmitrzak-Weglarz and J Kaprio and A Keski-Rahkonen and A Raevuori and {Van Furth}, E and Margarita Landt and James Hudson and Ted Reichborn-Kjennerud and Gun Knudsen and Palmiero Monteleone and Allan Kaplan and Adnreas Karwautz and Hakon Hakonarson and Wade Berrettini and Yiran Guo and Dong Li and Nicholas Schork and Gen Komaki and Tetsuya Ando and Hidetoshi Inoko and T{\~o}nu Esko and Krista Fischer and Katrin Mannik and Andres Metspalu and Jessica Baker and Roger Cone and Jennifer Dackor and Janeice DeSocio and Christopher Hilliard and Julie O'Toole and Jaques Pantel and Jin Szatkiewicz and Chrysecollo Taico and Stephanie Zerwas and Sara Trace and Oliver Davis and Sietske Helder and Katharina Buhren and Roland Burghardt and {de Zwaan}, Martina and Karin Egbert and Stefan Ehrlich and Beate Herpetz-Dahlmann and Wolfgang Herzog and Hartmut Imgart and Andre Scherag and Susann Scherag and Stephan Zipfell and Claudette Boni and Nicolas Ramoz and Audrey Versini and Marek Brandys and Unna Danner and {de Koval}, Carlien and Judith Hendricks and Bobby Koeleman and Roel Ophoff and Eric Strengman and {van Elburg}, Annemarie and Alice Bruson and Maurizio Clementi and Daniela Degortes and Monica Forzan and Elena Tenconi and Elisa Docampo and Georgia Escaramis and Susana Jimenez-Murcia and Jolanta Lissowska and Andrzej Rajewski and Neonila Szeszenia-Dabrowska and Agnieszka Slopien and Joanna Hauser and Lelia Karhunen and Ingrid Meulenbelt and Eline Slagboom and Alfonso Tortorella and Mario Maj and George Dedoussis and Dimitris Dikeos and Fragiskos Gonidakis and Konstantinos Tziouvas and Artemis Tsitsika and Hana Papezova and Lenka Slachtova and Debora Martaskova and James Kennedy and Robert Levitan and Zeynep Yilmaz and Julia Heumer and Doris Koubek and Elisabeth Merl and Gudrun Wagner and Paul Lichtenstein and Gerome Breen and Sarah Cohen-Woods and Anne Farmer and Peter McGuffin and Sven Cichon and Ina Giegling and Stefan Herms and Dan Rujescu and Stefan Schreiber and Wichmann, {H. Erich} and Christian Dina and Rob Sladek and Giovanni Gambaro and Nicole Soranzo and Antonio Julia and Sara Marsal and Raquel Rabionet and Valerie Gaborieau and Danielle Dick and Aarno Palotie and Samuli Ripatti and Elisabeth Widen and Ole Andreassen and Thomas Espeseth and Astri Lundervold and Ivar Reinvang and Vidar Steen and {Le Hellard}, Stephanie and Morten Mattingsdal and Ionna Ntalla and Vladimir Bencko and Lenka Faretova and Vladimir Janout and Marie Navratilova and Steven Gallinger and Dalila Pinto and Stephen Scherer and Harald Aschauer and Laura Carlberg and Alexandra Schosser and Lars Alfredsson and Bo Ding and Lars Klareskog and Leonid Padyukov and Chris Finan and Gursharan Kalsi and Marion Roberts and Darren Logan and Leena Peltonen and Graham Ritchie and Jeffrey Barrett and Xavier Estivill and Anke Hinney and Patrick Sullivan and David Collier and Eleftheria Zeggini and Cynthia Bulik",

year = "2014",

month = oct,

day = "1",

doi = "10.1038/mp.2013.187",

language = "English",

volume = "19",

pages = "1085--1094",

journal = "Molecular Psychiatry",

issn = "1476-5578",

publisher = "Nature",

number = "10",

}

Boraska, V, Franklin, C, Floyd, J, Thornton, M, Huckins, L, Southam, L, Rayner, N, Tachmazidou, I, Klump, K, Treasure, J, Lewis, C, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, H, Kas, M, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, E, Landt, M, Hudson, J, Reichborn-Kjennerud, T, Knudsen, G, Monteleone, P, Kaplan, A, Karwautz, A, Hakonarson, H, Berrettini, W, Guo, Y, Li, D, Schork, N, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Mannik, K, Metspalu, A, Baker, J, Cone, R, Dackor, J, DeSocio, J, Hilliard, C, O'Toole, J, Pantel, J, Szatkiewicz, J, Taico, C, Zerwas, S, Trace, S, Davis, O, Helder, S, Buhren, K, Burghardt, R, de Zwaan, M, Egbert, K, Ehrlich, S, Herpetz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfell, S, Boni, C, Ramoz, N, Versini, A, Brandys, M, Danner, U, de Koval, C, Hendricks, J, Koeleman, B, Ophoff, R, Strengman, E, van Elburg, A, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramis, G, Jimenez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, E, Tortorella, A, Maj, M, Dedoussis, G, Dikeos, D, Gonidakis, F, Tziouvas, K, Tsitsika, A, Papezova, H, Slachtova, L, Martaskova, D, Kennedy, J, Levitan, R, Yilmaz, Z, Heumer, J, Koubek, D, Merl, E, Wagner, G, Lichtenstein, P, Breen, G, Cohen-Woods, S, Farmer, A, McGuffin, P, Cichon, S, Giegling, I, Herms, S, Rujescu, D, Schreiber, S, Wichmann, HE, Dina, C, Sladek, R, Gambaro, G, Soranzo, N, Julia, A, Marsal, S, Rabionet, R, Gaborieau, V, Dick, D, Palotie, A, Ripatti, S, Widen, E, Andreassen, O, Espeseth, T, Lundervold, A, Reinvang, I, Steen, V, Le Hellard, S, Mattingsdal, M, Ntalla, I, Bencko, V, Faretova, L, Janout, V, Navratilova, M, Gallinger, S, Pinto, D, Scherer, S, Aschauer, H, Carlberg, L, Schosser, A, Alfredsson, L, Ding, B, Klareskog, L, Padyukov, L, Finan, C, Kalsi, G, Roberts, M, Logan, D, Peltonen, L, Ritchie, G, Barrett, J, Estivill, X, Hinney, A, Sullivan, P, Collier, D, Zeggini, E & Bulik, C 2014, 'A genome-wide association study of anorexia nervosa', MOLECULAR PSYCHIATRY, vol. 19, no. 10, pp. 1085-1094. https://doi.org/10.1038/mp.2013.187

TY - JOUR

T1 - A genome-wide association study of anorexia nervosa

AU - Boraska, V

AU - Franklin, C

AU - Floyd, J

AU - Thornton, M

AU - Huckins, L

AU - Southam, L

AU - Rayner, N

AU - Tachmazidou, I

AU - Klump, K

AU - Treasure, J

AU - Lewis, C

AU - Schmidt, U

AU - Tozzi, F

AU - Kiezebrink, K

AU - Hebebrand, J

AU - Gorwood, P

AU - Adan, H

AU - Kas, M

AU - Favaro, A

AU - Santonastaso, P

AU - Fernández-Aranda, F

AU - Gratacos, M

AU - Rybakowski, F

AU - Dmitrzak-Weglarz, M

AU - Kaprio, J

AU - Keski-Rahkonen, A

AU - Raevuori, A

AU - Van Furth, E

AU - Landt, Margarita

AU - Hudson, James

AU - Reichborn-Kjennerud, Ted

AU - Knudsen, Gun

AU - Monteleone, Palmiero

AU - Kaplan, Allan

AU - Karwautz, Adnreas

AU - Hakonarson, Hakon

AU - Berrettini, Wade

AU - Guo, Yiran

AU - Li, Dong

AU - Schork, Nicholas

AU - Komaki, Gen

AU - Ando, Tetsuya

AU - Inoko, Hidetoshi

AU - Esko, Tõnu

AU - Fischer, Krista

AU - Mannik, Katrin

AU - Metspalu, Andres

AU - Baker, Jessica

AU - Cone, Roger

AU - Dackor, Jennifer

AU - DeSocio, Janeice

AU - Hilliard, Christopher

AU - O'Toole, Julie

AU - Pantel, Jaques

AU - Szatkiewicz, Jin

AU - Taico, Chrysecollo

AU - Zerwas, Stephanie

AU - Trace, Sara

AU - Davis, Oliver

AU - Helder, Sietske

AU - Buhren, Katharina

AU - Burghardt, Roland

AU - de Zwaan, Martina

AU - Egbert, Karin

AU - Ehrlich, Stefan

AU - Herpetz-Dahlmann, Beate

AU - Herzog, Wolfgang

AU - Imgart, Hartmut

AU - Scherag, Andre

AU - Scherag, Susann

AU - Zipfell, Stephan

AU - Boni, Claudette

AU - Ramoz, Nicolas

AU - Versini, Audrey

AU - Brandys, Marek

AU - Danner, Unna

AU - de Koval, Carlien

AU - Hendricks, Judith

AU - Koeleman, Bobby

AU - Ophoff, Roel

AU - Strengman, Eric

AU - van Elburg, Annemarie

AU - Bruson, Alice

AU - Clementi, Maurizio

AU - Degortes, Daniela

AU - Forzan, Monica

AU - Tenconi, Elena

AU - Docampo, Elisa

AU - Escaramis, Georgia

AU - Jimenez-Murcia, Susana

AU - Lissowska, Jolanta

AU - Rajewski, Andrzej

AU - Szeszenia-Dabrowska, Neonila

AU - Slopien, Agnieszka

AU - Hauser, Joanna

AU - Karhunen, Lelia

AU - Meulenbelt, Ingrid

AU - Slagboom, Eline

AU - Tortorella, Alfonso

AU - Maj, Mario

AU - Dedoussis, George

AU - Dikeos, Dimitris

AU - Gonidakis, Fragiskos

AU - Tziouvas, Konstantinos

AU - Tsitsika, Artemis

AU - Papezova, Hana

AU - Slachtova, Lenka

AU - Martaskova, Debora

AU - Kennedy, James

AU - Levitan, Robert

AU - Yilmaz, Zeynep

AU - Heumer, Julia

AU - Koubek, Doris

AU - Merl, Elisabeth

AU - Wagner, Gudrun

AU - Lichtenstein, Paul

AU - Breen, Gerome

AU - Cohen-Woods, Sarah

AU - Farmer, Anne

AU - McGuffin, Peter

AU - Cichon, Sven

AU - Giegling, Ina

AU - Herms, Stefan

AU - Rujescu, Dan

AU - Schreiber, Stefan

AU - Wichmann, H. Erich

AU - Dina, Christian

AU - Sladek, Rob

AU - Gambaro, Giovanni

AU - Soranzo, Nicole

AU - Julia, Antonio

AU - Marsal, Sara

AU - Rabionet, Raquel

AU - Gaborieau, Valerie

AU - Dick, Danielle

AU - Palotie, Aarno

AU - Ripatti, Samuli

AU - Widen, Elisabeth

AU - Andreassen, Ole

AU - Espeseth, Thomas

AU - Lundervold, Astri

AU - Reinvang, Ivar

AU - Steen, Vidar

AU - Le Hellard, Stephanie

AU - Mattingsdal, Morten

AU - Ntalla, Ionna

AU - Bencko, Vladimir

AU - Faretova, Lenka

AU - Janout, Vladimir

AU - Navratilova, Marie

AU - Gallinger, Steven

AU - Pinto, Dalila

AU - Scherer, Stephen

AU - Aschauer, Harald

AU - Carlberg, Laura

AU - Schosser, Alexandra

AU - Alfredsson, Lars

AU - Ding, Bo

AU - Klareskog, Lars

AU - Padyukov, Leonid

AU - Finan, Chris

AU - Kalsi, Gursharan

AU - Roberts, Marion

AU - Logan, Darren

AU - Peltonen, Leena

AU - Ritchie, Graham

AU - Barrett, Jeffrey

AU - Estivill, Xavier

AU - Hinney, Anke

AU - Sullivan, Patrick

AU - Collier, David

AU - Zeggini, Eleftheria

AU - Bulik, Cynthia

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 × 10-7) in SOX2OT and rs17030795 (P = 5.84 × 10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 × 10-6) between CUL3 and FAM124B and rs1886797 (P = 8.05 × 10-6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4 × 10-6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

AB - Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 × 10-7) in SOX2OT and rs17030795 (P = 5.84 × 10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 × 10-6) between CUL3 and FAM124B and rs1886797 (P = 8.05 × 10-6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P = 4 × 10-6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

KW - Anorexia nervosa

KW - Body mass index

KW - Eating disorders

KW - Genome-wide association study

KW - GWAS

KW - Metabolic

UR - http://www.scopus.com/inward/record.url?scp=84905856652&partnerID=8YFLogxK

U2 - 10.1038/mp.2013.187

DO - 10.1038/mp.2013.187

M3 - Article

SN - 1476-5578

VL - 19

SP - 1085

EP - 1094

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

A genome-wide association study of anorexia nervosa

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this