Molecular Genetics of Obsessive‐Compulsive Disorder

Abstract

Genetic association studies of obsessive‐compulsive disorder (OCD) have yielded inconsistent findings because those studies have tended to have small sample sizes and low statistical power, thereby making it difficult to reliably detect small genetic effects. Meta‐analysis combines individual studies thereby increasing the power to detect small effects. Meta‐analysis suggests that OCD is associated with serotonin‐related polymorphisms (5‐HTTLPR and HTR2A) and, in males only, polymorphisms involving catecholamine modulation (COMT and MAOA). There is also suggestive evidence that many other polymorphisms are associated with OCD. Effects of individual polymorphisms are small, suggesting that OCD is shaped by multiple genes that each make small, incremental contributions to the risk of developing the disorder. Twin studies show that there are genetic similarities and differences across OCD subtypes (early versus late onset) and across major types of OCD symptoms (e.g. washing, checking, and ordering). Genetic association studies of specific subtypes and symptoms may advance our understanding of OCD.

Key Concepts:

  • Genetic association studies, typically with small sample sizes, tend to fail to reliably identify OCD‐related polymorphisms, because genetic effects tend to be small.

  • Meta‐analysis, combining numerous genetic studies, indicates that numerous genes play a small, incremental role in the risk of developing OCD.

  • The genes most robustly associated with OCD are serotonin‐related and, in males, are those broadly involved in catecholamine modulation.

  • There is suggestive evidence that other genes are involved.

  • Haplotypes associated with glutamate regulation may also be associated with OCD.

  • Twin studies can facilitate molecular genetic research by shedding light on aetiologic differences among OCD symptoms and subtypes.

  • Twin research shows that some genetic factors are common to all OCD symptoms, whereas others are symptom‐specific.

  • Genetic association studies of specific subtypes and symptoms may advance our understanding of OCD.

Keywords: obsessive‐compulsive disorder; obsessions; compulsions; genetics; genetic association studies; twins; behavioural genetics; haplotypes; genome‐wide association; meta‐analysis

Figure 1.

Meta‐regression predicting nonshared environment from age at assessment. Circle diameters are proportional to the weights assigned to the samples. Reproduced from Taylor (). © Elsevier.

Figure 2.

Proportions of variance in OC symptom severity due to general‐ etiologic factors (common to all OC symptoms) or symptom‐specific etiologic factors. (a) Shows the relative importance of general and specific additive genetic factors and (b) shows the relative importance of general and specific environmental factors. Reproduced from Taylor (). © Elsevier.

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Further Reading

Haworth CM and Plomin R (2010) Quantitative genetics in the era of molecular genetics: learning abilities and disabilities as an example. Journal of the American Academy of Child and Adolescent Psychiatry 49: 783–793.

Kendler KS (2012) The dappled nature of causes of psychiatric illness: replacing the organic‐functional/hardware‐software dichotomy with empirically based pluralism. Molecular Psychiatry 17: 377–388.

Kendler KS (2013) What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. Molecular Psychiatry 18: 1058–1066.

Kendler KS and Prescott CA (2006) Genes, Environment, and Psychopathology: Understanding the Causes of Psychiatric and Substance Use Disorders. New York: Guilford.

Taylor S (2011) Early versus late onset obsessive‐compulsive disorder: evidence for distinct subtypes. Clinical Psychology Review 31: 1083–1100.

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Taylor, Steven(May 2014) Molecular Genetics of Obsessive‐Compulsive Disorder. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023575]