Bipolar disorder with comorbid binge eating history: A genome-wide association study implicates APOB

Stacey J Winham, Alfredo B. Cuellar-Barboza, Susan L. McElroy, Alfredo Oliveros, Scott Crow, Colin L. Colby, Doo Sup Choi, Mohit Chauhan, Mark A Frye, Joanna M Biernacka

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. Methods Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. Results Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. Limitations Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. Conclusions This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of Affective Disorders
Volume165
DOIs
StatePublished - Aug 20 2014

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Bulimia
Genome-Wide Association Study
Bipolar Disorder
Single Nucleotide Polymorphism
History
Genetic Research
Information Services
Feeding Behavior
Risk-Taking
Longitudinal Studies
Meta-Analysis
Software
Eating

Keywords

  • APOB
  • Binge eating
  • Bipolar disorder
  • Genome-wide association study (GWAS)
  • Network analysis
  • Phenotypic subtypes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology
  • Medicine(all)

Cite this

Bipolar disorder with comorbid binge eating history : A genome-wide association study implicates APOB. / Winham, Stacey J; Cuellar-Barboza, Alfredo B.; McElroy, Susan L.; Oliveros, Alfredo; Crow, Scott; Colby, Colin L.; Choi, Doo Sup; Chauhan, Mohit; Frye, Mark A; Biernacka, Joanna M.

In: Journal of Affective Disorders, Vol. 165, 20.08.2014, p. 151-158.

Research output: Contribution to journalArticle

Winham, Stacey J ; Cuellar-Barboza, Alfredo B. ; McElroy, Susan L. ; Oliveros, Alfredo ; Crow, Scott ; Colby, Colin L. ; Choi, Doo Sup ; Chauhan, Mohit ; Frye, Mark A ; Biernacka, Joanna M. / Bipolar disorder with comorbid binge eating history : A genome-wide association study implicates APOB. In: Journal of Affective Disorders. 2014 ; Vol. 165. pp. 151-158.
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abstract = "Background Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. Methods Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. Results Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. Limitations Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. Conclusions This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.",
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T2 - A genome-wide association study implicates APOB

AU - Winham, Stacey J

AU - Cuellar-Barboza, Alfredo B.

AU - McElroy, Susan L.

AU - Oliveros, Alfredo

AU - Crow, Scott

AU - Colby, Colin L.

AU - Choi, Doo Sup

AU - Chauhan, Mohit

AU - Frye, Mark A

AU - Biernacka, Joanna M

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N2 - Background Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. Methods Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. Results Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. Limitations Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. Conclusions This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.

AB - Background Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. Methods Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. Results Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. Limitations Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. Conclusions This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.

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