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 - Davis, Oliver S.P.
AU - Soranzo, Nicole
AU - Mitchell, James
AU - Bergen, Andrew W.
AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium
AU - Price Foundation Collaborative Group
PY - 2017/9/17
Y1 - 2017/9/17
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 (Academic Journal)
C2 - 28630421
AN - SCOPUS:85021082843
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
M1 - 3847
ER -