Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder

Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

Abstract

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Anorexia Nervosa
Phenotype
Single Nucleotide Polymorphism
Psychiatry
Genome-Wide Association Study
Basal Ganglia
Bipolar Disorder
Meta-Analysis
Triglycerides
Body Mass Index
Genome
Gene Expression
Neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium (Accepted/In press). Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder. Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0115-4

Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder. / Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Molecular Psychiatry, 01.01.2018.

Research output: Contribution to journalArticle

Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium 2018, 'Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder', Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0115-4
Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium. Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder. Molecular Psychiatry. 2018 Jan 1. https://doi.org/10.1038/s41380-018-0115-4
Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium. / Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder. In: Molecular Psychiatry. 2018.
@article{f3830576da13483b85f4fe624cb89585,
title = "Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder",
abstract = "Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.",
author = "{Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium} and Zeynep Yilmaz and Matthew Halvorsen and Julien Bryois and Dongmei Yu and Thornton, {Laura M.} and Stephanie Zerwas and Nadia Micali and Rainald Moessner and Burton, {Christie L.} and Gwyneth Zai and Lauren Erdman and Kas, {Martien J.} and Arnold, {Paul D.} and Davis, {Lea K.} and Knowles, {James A.} and Gerome Breen and Scharf, {Jeremiah M.} and Gerald Nestadt and Mathews, {Carol A.} and Bulik, {Cynthia M.} and Manuel Mattheisen and Crowley, {James J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1038/s41380-018-0115-4",
language = "English (US)",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder

AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Yilmaz, Zeynep

AU - Halvorsen, Matthew

AU - Bryois, Julien

AU - Yu, Dongmei

AU - Thornton, Laura M.

AU - Zerwas, Stephanie

AU - Micali, Nadia

AU - Moessner, Rainald

AU - Burton, Christie L.

AU - Zai, Gwyneth

AU - Erdman, Lauren

AU - Kas, Martien J.

AU - Arnold, Paul D.

AU - Davis, Lea K.

AU - Knowles, James A.

AU - Breen, Gerome

AU - Scharf, Jeremiah M.

AU - Nestadt, Gerald

AU - Mathews, Carol A.

AU - Bulik, Cynthia M.

AU - Mattheisen, Manuel

AU - Crowley, James J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

AB - Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

UR - http://www.scopus.com/inward/record.url?scp=85052502009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052502009&partnerID=8YFLogxK

U2 - 10.1038/s41380-018-0115-4

DO - 10.1038/s41380-018-0115-4

M3 - Article

C2 - 30087453

AN - SCOPUS:85052502009

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -