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 crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (r g = 0.49 ± 0.13, p = 9.07x10 -7 ) and a sizable SNP heritability (SNP h 2 = 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., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, 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.

Exploring the ways in which COVID‐19 and lockdown has affected the lives of adult patients with anorexia nervosa and their carers

“…The findings that patients reported heightened general anxiety, health anxiety and increased OCD behaviours as a direct impact of COVID‐19 was expected, given previous research demonstrating the strong link between anxiety traits, particularly OCD and AN (Levinson et al, 2019; Yilmaz et al, 2018). References to the role of media in amplifying anxiety echoes concerns expressed over repeated media consumption and health messaging around COVID‐19 for vulnerable populations (Holmes et al, 2020).…”

Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs

“…The precise etiology of OCD remains unclear, but accumulating evidence suggests pivotal roles of structural abnormalities and/ or dysregulations of synaptogenesis and neuronal circuits within particular regions of the brain in both OCD patients and affected animals [7,[9][10][11][12]. Genetic analyses, including genome-wide association studies (GWAS), have been conducted to identify genes underlying risk of OCD in human populations [13][14][15]. However, results have been inconsistent, likely due to the phenotypic, genetic and etiologic heterogeneity of the disorder [16,17].…”

Transcriptomic analysis of dystonia-associated genes reveals functional convergence within specific cell types and shared neurobiology with psychiatric disorders

“…Notably, integration of GWAS-identified risk variants for obsessive-compulsive disorder and schizophrenia together with recent transcriptomic analyses have implicated MSNs in the neurobiology of these neuropsychiatric diseases (Skene et al, 2018;Yilmaz et al, 2018). We too observed an enrichment of obsessive-compulsive disorder and schizophrenia heritability in the MSN-related "cyan" putamen module, suggesting that dysfunction of MSN synaptic activity, resulting from different types of genetic insult, may represent an overlap in the biology of dystonia and these neuropsychiatric conditions.…”