Inheritance Pattern of Obsessive-Compulsive Disorder
OCD follows a polygenic inheritance pattern with variable expressivity, not autosomal dominant, mitochondrial, or X-linked recessive inheritance. 1
Genetic Architecture
The genetic basis of OCD is fundamentally polygenic, meaning risk is distributed across many genetic variants throughout the genome rather than being caused by a single gene. 1 This has been consistently demonstrated through multiple lines of evidence:
Twin studies show that additive genetic effects account for approximately 40% of variance in obsessive-compulsive symptoms, with the remaining variance primarily attributed to non-shared environmental factors (~51%). 1
Common inherited genetic variation (minor allele frequency ≥0.01) accounts for most of the heritable variation in OCD, with narrow-sense heritability estimated at 29%. 2
The disorder is influenced by a large number of genetic loci across the genome and across different allele frequency bins, consistent with the "infinitesimal model" or "polygenic model." 2
Why Not Other Inheritance Patterns
Autosomal dominant with complete penetrance is definitively ruled out because:
- OCD does not show the characteristic 50% transmission rate to offspring expected with dominant inheritance 3
- Segregation analysis studies have suggested both major single gene effects and polygenic hypotheses, but the overwhelming evidence supports polygenic architecture 4
- The 40% heritability estimate is far lower than would be expected with complete penetrance 1
Mitochondrial and X-linked recessive patterns are not supported by family studies, which show no maternal-only transmission pattern or sex-linked distribution characteristic of these inheritance modes. 3
Variable Expressivity
The polygenic nature of OCD naturally leads to variable expressivity:
- Different OCD symptom dimensions (contamination, symmetry, etc.) have both shared and unique genetic risks 3
- Early-onset OCD with tics may have higher heritability than other OCD subtypes 1
- Polygenic risk scores show quantitative and qualitative heterogeneity across different comorbid OCD subgroups 5
Clinical Implications for Genetic Counseling
The 40% heritability from additive genetic effects provides a practical estimate for discussing familial risk with patients and families. 1 This means that genetic factors contribute substantially but not deterministically to OCD risk, with environmental factors and gene-environment interactions playing important complementary roles. 1, 3