A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

Bipolar Genome Study (BiGS)

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. Methods We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). Results The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10-8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10-6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10-7 and 4.3×10-6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. Limitations While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. Conclusions These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.

Original languageEnglish (US)
Article number7712
Pages (from-to)141-149
Number of pages9
JournalJournal of Affective Disorders
Volume189
DOIs
StatePublished - Jan 1 2016

Fingerprint

Genome-Wide Association Study
Bipolar Disorder
Comorbidity
Genome
Mood Disorders
Sample Size
Genes
Feeding and Eating Disorders
Chromosomes

Keywords

  • Bipolar disorder
  • Comorbidity
  • Eating disorders
  • Genome-wide association (GWAS)
  • SOX2-OT

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region. / Bipolar Genome Study (BiGS).

In: Journal of Affective Disorders, Vol. 189, 7712, 01.01.2016, p. 141-149.

Research output: Contribution to journalArticle

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title = "A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region",
abstract = "Background Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. Methods We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). Results The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10-8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10-6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10-7 and 4.3×10-6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. Limitations While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. Conclusions These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.",
keywords = "Bipolar disorder, Comorbidity, Eating disorders, Genome-wide association (GWAS), SOX2-OT",
author = "{Bipolar Genome Study (BiGS)} and Xiaohua Liu and Kelsoe, {John R.} and Greenwood, {Tiffany A.} and Kelsoe, {John R.} and Green-Wood, {Tiffany A.} and Nievergelt, {Caroline M.} and Rebecca McKinney and Shilling, {Paul D.} and Smith, {Erin N.} and Schork, {Nicholas J.} and Bloss, {Cinnamon S.} and John Nurnberger and Howard Edenberg and Tatiana Foroud and Koller, {Daniel L.} and Gershon, {Elliot S.} and Chunyu Liu and Badner, {Judith A.} and Scheftner, {William A.} and Lawson, {William B.} and Nwulia, {Evaristus A.} and Maria Hipolito and William Coryell and Potash, {James B.} and John Rice and William Byerley and McMahon, {Francis J.} and Schulze, {Thomas G.} and Berrettini, {Wade H.} and Zandi, {Peter P.} and Mahon, {Pamela B.} and McInnis, {Melvin G.} and Sebastian Z{\"o}llner and Peng Zhang and Craig, {David W.} and Szabolcs Szelinger and Barrett, {Thomas B.}",
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T1 - A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

AU - Bipolar Genome Study (BiGS)

AU - Liu, Xiaohua

AU - Kelsoe, John R.

AU - Greenwood, Tiffany A.

AU - Kelsoe, John R.

AU - Green-Wood, Tiffany A.

AU - Nievergelt, Caroline M.

AU - McKinney, Rebecca

AU - Shilling, Paul D.

AU - Smith, Erin N.

AU - Schork, Nicholas J.

AU - Bloss, Cinnamon S.

AU - Nurnberger, John

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Koller, Daniel L.

AU - Gershon, Elliot S.

AU - Liu, Chunyu

AU - Badner, Judith A.

AU - Scheftner, William A.

AU - Lawson, William B.

AU - Nwulia, Evaristus A.

AU - Hipolito, Maria

AU - Coryell, William

AU - Potash, James B.

AU - Rice, John

AU - Byerley, William

AU - McMahon, Francis J.

AU - Schulze, Thomas G.

AU - Berrettini, Wade H.

AU - Zandi, Peter P.

AU - Mahon, Pamela B.

AU - McInnis, Melvin G.

AU - Zöllner, Sebastian

AU - Zhang, Peng

AU - Craig, David W.

AU - Szelinger, Szabolcs

AU - Barrett, Thomas B.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. Methods We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). Results The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10-8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10-6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10-7 and 4.3×10-6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. Limitations While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. Conclusions These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.

AB - Background Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. Methods We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). Results The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10-8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10-6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10-7 and 4.3×10-6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. Limitations While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. Conclusions These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.

KW - Bipolar disorder

KW - Comorbidity

KW - Eating disorders

KW - Genome-wide association (GWAS)

KW - SOX2-OT

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JO - Journal of Affective Disorders

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