A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

Dong Li; Xiao Chang; John J. Connolly; Lifeng Tian; Yichuan Liu; Elizabeth J. Bhoj; Nora Robinson; Debra Abrams; Yun R. Li; Jonathan P. Bradfield; Cecilia E. Kim; Jin Li; Fengxiang Wang; James Snyder; Maria Lemma; Cuiping Hou; Zhi Wei; Yiran Guo; Haijun Qiu; Frank D. Mentch; Kelly A. Thomas; Rosetta M. Chiavacci; Roger Cone; Bingshan Li; Patrick A. Sleiman; Eating Disorder Working Group of the Psychiatric Genomics Consortium; Hakon Hakonarson; Vesna Boraska Perica; Christopher S. Franklin; James A.B. Floyd; Laura M. Thornton; Laura M. Huckins; Lorraine Southam; N. William Rayner; Ioanna Tachmazidou; Ulrike Schmidt; Federica Tozzi; Kirsty Kiezebrink; Johannes Hebebrand; Philip Gorwood; Roger A.H. Adan; Martien J.H. Kas; Angela Favaro; Paolo Santonastaso; Fernando Fernánde-Aranda; Monica Gratacos; Filip Rybakowski; Oliver S.P. Davis; Gursharan Kalsi; Marion Roberts; Janet Treasure

doi:10.1038/s41598-017-01674-8

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

Dong Li^*, Xiao Chang, John J. Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J. Bhoj, Nora Robinson, Debra Abrams, Yun R. Li, Jonathan P. Bradfield, Cecilia E. Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Yiran Guo, Haijun Qiu, Frank D. MentchKelly A. Thomas, Rosetta M. Chiavacci, Roger Cone, Bingshan Li, Patrick A. Sleiman, Eating Disorder Working Group of the Psychiatric Genomics Consortium, Hakon Hakonarson, Vesna Boraska Perica, Christopher S. Franklin, James A.B. Floyd, Laura M. Thornton, Laura M. Huckins, Lorraine Southam, N. William Rayner, Ioanna Tachmazidou, Ulrike Schmidt, Federica Tozzi, Kirsty Kiezebrink, Johannes Hebebrand, Philip Gorwood, Roger A.H. Adan, Martien J.H. Kas, Angela Favaro, Paolo Santonastaso, Fernando Fernánde-Aranda, Monica Gratacos, Filip Rybakowski, Oliver S.P. Davis, Gursharan Kalsi, Marion Roberts, Janet Treasure

^*Corresponding author for this work

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

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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
Article number	3847
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-01674-8
Publication status	Published - 1 Dec 2017

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Li, D., Chang, X., Connolly, J. J., Tian, L., Liu, Y., Bhoj, E. J., Robinson, N., Abrams, D., Li, Y. R., Bradfield, J. P., Kim, C. E., Li, J., Wang, F., Snyder, J., Lemma, M., Hou, C., Wei, Z., Guo, Y., Qiu, H., ... Treasure, J. (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7(1), Article 3847. https://doi.org/10.1038/s41598-017-01674-8

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title = "A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling",

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.",

author = "Dong Li and Xiao Chang and Connolly, {John J.} and Lifeng Tian and Yichuan Liu and Bhoj, {Elizabeth J.} and Nora Robinson and Debra Abrams and Li, {Yun R.} and Bradfield, {Jonathan P.} and Kim, {Cecilia E.} and Jin Li and Fengxiang Wang and James Snyder and Maria Lemma and Cuiping Hou and Zhi Wei and Yiran Guo and Haijun Qiu and Mentch, {Frank D.} and Thomas, {Kelly A.} and Chiavacci, {Rosetta M.} and Roger Cone and Bingshan Li and Sleiman, {Patrick A.} and {Eating Disorder Working Group of the Psychiatric Genomics Consortium} and Hakon Hakonarson and Perica, {Vesna Boraska} and Franklin, {Christopher S.} and Floyd, {James A.B.} and Thornton, {Laura M.} and Huckins, {Laura M.} and Lorraine Southam and Rayner, {N. William} and Ioanna Tachmazidou and Ulrike Schmidt and Federica Tozzi and Kirsty Kiezebrink and Johannes Hebebrand and Philip Gorwood and Adan, {Roger A.H.} and Kas, {Martien J.H.} and Angela Favaro and Paolo Santonastaso and Fernando Fern{\'a}nde-Aranda and Monica Gratacos and Filip Rybakowski and Davis, {Oliver S.P.} and Gursharan Kalsi and Marion Roberts and Janet Treasure",

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doi = "10.1038/s41598-017-01674-8",

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Li, D, Chang, X, Connolly, JJ, Tian, L, Liu, Y, Bhoj, EJ, Robinson, N, Abrams, D, Li, YR, Bradfield, JP, Kim, CE, Li, J, Wang, F, Snyder, J, Lemma, M, Hou, C, Wei, Z, Guo, Y, Qiu, H, Mentch, FD, Thomas, KA, Chiavacci, RM, Cone, R, Li, B, Sleiman, PA, Eating Disorder Working Group of the Psychiatric Genomics Consortium, Hakonarson, H, Perica, VB, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernánde-Aranda, F, Gratacos, M, Rybakowski, F, Davis, OSP , Kalsi, G , Roberts, M & Treasure, J 2017, 'A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling', Scientific Reports, vol. 7, no. 1, 3847. https://doi.org/10.1038/s41598-017-01674-8

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 - Eating Disorder Working Group of the Psychiatric Genomics Consortium

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 - Davis, Oliver S.P.

AU - Kalsi, Gursharan

AU - Roberts, Marion

AU - Treasure, Janet

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

AN - SCOPUS:85021082843

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 3847

ER -

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

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