Abstract
We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
| Original language | English (US) |
|---|---|
| Article number | 3847 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2017 |
ASJC Scopus subject areas
- General
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A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. / Li, Dong; Chang, Xiao; Connolly, John J.; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J.; Robinson, Nora; Abrams, Debra; Li, Yun R.; Bradfield, Jonathan P.; Kim, Cecilia E.; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Cone, Roger; Li, Bingshan; Sleiman, Patrick A.; Hakonarson, Hakon; Perica, Vesna Boraska; Franklin, Christopher S.; Floyd, James A.B.; Thornton, Laura M.; Huckins, Laura M.; Southam, Lorraine; Rayner, N. William; Tachmazidou, Ioanna; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger A.H.; Kas, Martien J.H.; Favaro, Angela; Santonastaso, Paolo; Fernánde-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori-Helkamaa, Anu; Furth, Eric F.Van; Slof-Opt Landt, Margarita C.T.; Hudson, James I.; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S.; Monteleone, Palmiero; Karwautz, Andreas; Berrettini, Wade H.; Schork, Nicholas J.; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Toñu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H.; DeSocio, Janiece E.; Hilliard, Christopher E.; O'Toole, Julie K.; Pantel, Jacques; Szatkiewicz, Jin P.; Zerwas, Stephanie; Davis, Oliver S.P.; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; De Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Danner, Unna N.; Hendriks, Judith; Koeleman, Bobby P.C.; Ophoff, Roel A.; Strengman, Eric; Van Elburg, Annemarie A.; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P. Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; DIkeos, DImitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H. Erich; DIna, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; DIck, Danielle M.; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A.; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M.; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen W.; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; DIng, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Barrett, Jeff C.; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F.; Zeggini, Eleftheria; Bulik, Cynthia M.; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M.; Halmi, Katherine A.; Johnson, Craig; Kaplan, Allan S.; La Via, Maria C.; Mitchell, James; Strober, Michael; Rotondo, Alessandro; Treasure, Janet; Woodside, D. Blake; Keel, Pamela K.; Klump, Kelly L.; Lilenfeld, Lisa; Bergen, Andrew W.; Kaye, Walter; Magistretti, Pierre.
In: Scientific Reports, Vol. 7, No. 1, 3847, 01.12.2017.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
AU - Li, Dong
AU - Chang, Xiao
AU - Connolly, John J.
AU - Tian, Lifeng
AU - Liu, Yichuan
AU - Bhoj, Elizabeth J.
AU - Robinson, Nora
AU - Abrams, Debra
AU - Li, Yun R.
AU - Bradfield, Jonathan P.
AU - Kim, Cecilia E.
AU - Li, Jin
AU - Wang, Fengxiang
AU - Snyder, James
AU - Lemma, Maria
AU - Hou, Cuiping
AU - Wei, Zhi
AU - Guo, Yiran
AU - Qiu, Haijun
AU - Mentch, Frank D.
AU - Thomas, Kelly A.
AU - Chiavacci, Rosetta M.
AU - Cone, Roger
AU - Li, Bingshan
AU - Sleiman, Patrick A.
AU - Hakonarson, Hakon
AU - Perica, Vesna Boraska
AU - Franklin, Christopher S.
AU - Floyd, James A.B.
AU - Thornton, Laura M.
AU - Huckins, Laura M.
AU - Southam, Lorraine
AU - Rayner, N. William
AU - Tachmazidou, Ioanna
AU - Schmidt, Ulrike
AU - Tozzi, Federica
AU - Kiezebrink, Kirsty
AU - Hebebrand, Johannes
AU - Gorwood, Philip
AU - Adan, Roger A.H.
AU - Kas, Martien J.H.
AU - Favaro, Angela
AU - Santonastaso, Paolo
AU - Fernánde-Aranda, Fernando
AU - Gratacos, Monica
AU - Rybakowski, Filip
AU - Dmitrzak-Weglarz, Monika
AU - Kaprio, Jaakko
AU - Keski-Rahkonen, Anna
AU - Raevuori-Helkamaa, Anu
AU - Furth, Eric F.Van
AU - Slof-Opt Landt, Margarita C.T.
AU - Hudson, James I.
AU - Reichborn-Kjennerud, Ted
AU - Knudsen, Gun Peggy S.
AU - Monteleone, Palmiero
AU - Karwautz, Andreas
AU - Berrettini, Wade H.
AU - Schork, Nicholas J.
AU - Ando, Tetsuya
AU - Inoko, Hidetoshi
AU - Esko, Toñu
AU - Fischer, Krista
AU - Männik, Katrin
AU - Metspalu, Andres
AU - Baker, Jessica H.
AU - DeSocio, Janiece E.
AU - Hilliard, Christopher E.
AU - O'Toole, Julie K.
AU - Pantel, Jacques
AU - Szatkiewicz, Jin P.
AU - Zerwas, Stephanie
AU - Davis, Oliver S.P.
AU - Helder, Sietske
AU - Bühren, Katharina
AU - Burghardt, Roland
AU - De Zwaan, Martina
AU - Egberts, Karin
AU - Ehrlich, Stefan
AU - Herpertz-Dahlmann, Beate
AU - Herzog, Wolfgang
AU - Imgart, Hartmut
AU - Scherag, André
AU - Zipfel, Stephan
AU - Boni, Claudette
AU - Ramoz, Nicolas
AU - Versini, Audrey
AU - Danner, Unna N.
AU - Hendriks, Judith
AU - Koeleman, Bobby P.C.
AU - Ophoff, Roel A.
AU - Strengman, Eric
AU - Van Elburg, Annemarie A.
AU - Bruson, Alice
AU - Clementi, Maurizio
AU - Degortes, Daniela
AU - Forzan, Monica
AU - Tenconi, Elena
AU - Docampo, Elisa
AU - Escaramís, Geòrgia
AU - Jiménez-Murcia, Susana
AU - Lissowska, Jolanta
AU - Rajewski, Andrzej
AU - Szeszenia-Dabrowska, Neonila
AU - Slopien, Agnieszka
AU - Hauser, Joanna
AU - Karhunen, Leila
AU - Meulenbelt, Ingrid
AU - Slagboom, P. 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 L.
AU - Levitan, Robert D.
AU - Yilmaz, Zeynep
AU - Huemer, 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 M.
AU - Palotie, Aarno
AU - Ripatti, Samuli
AU - Widén, Elisabeth
AU - Andreassen, Ole A.
AU - Espeseth, Thomas
AU - Lundervold, Astri
AU - Reinvang, Ivar
AU - Steen, Vidar M.
AU - Le Hellard, Stephanie
AU - Mattingsdal, Morten
AU - Ntalla, Ioanna
AU - Bencko, Vladimir
AU - Foretova, Lenka
AU - Janout, Vladimir
AU - Navratilova, Marie
AU - Gallinger, Steven
AU - Pinto, Dalila
AU - Scherer, Stephen W.
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 - Barrett, Jeff C.
AU - Estivill, Xavier
AU - Hinney, Anke
AU - Sullivan, Patrick F.
AU - Zeggini, Eleftheria
AU - Bulik, Cynthia M.
AU - Brandt, Harry
AU - Crawford, Steve
AU - Crow, Scott
AU - Fichter, Manfred M.
AU - Halmi, Katherine A.
AU - Johnson, Craig
AU - Kaplan, Allan S.
AU - La Via, Maria C.
AU - Mitchell, James
AU - Strober, Michael
AU - Rotondo, Alessandro
AU - Treasure, Janet
AU - Woodside, D. Blake
AU - Keel, Pamela K.
AU - Klump, Kelly L.
AU - Lilenfeld, Lisa
AU - Bergen, Andrew W.
AU - Kaye, Walter
AU - Magistretti, Pierre
PY - 2017/12/1
Y1 - 2017/12/1
N2 - We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
AB - We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
UR - http://www.scopus.com/inward/record.url?scp=85021082843&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-01674-8
DO - 10.1038/s41598-017-01674-8
M3 - Article
C2 - 28630421
AN - SCOPUS:85021082843
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3847
ER -