| Gene/Locus | Chromosome Location | Function/Description | Evidence Type (GWAS/TWAS/PWAS) | P-value or significance | Key Findings |
|---|---|---|---|---|---|
| OCD GWAS meta-analysis summary | Genome-wide | Large-scale common-variant architecture of OCD | GWAS | 30 independent genome-wide significant loci in 53,660 cases and 2,044,417 controls; 1,672 SNPs exceeded genome-wide significance; threshold P < 5×10⁻⁸ (pqac-00000003, pqac-00000006) | Largest reported OCD GWAS identified 30 loci, substantially expanding prior findings and supporting a highly polygenic architecture (pqac-00000003, pqac-00000006) |
| Polygenic architecture | Genome-wide | Aggregate common-variant contribution to OCD risk | GWAS / MiXeR | ~11,500 causal variants (SE 607) explain 90% of OCD SNP-based heritability (pqac-00000006) | Indicates OCD risk is distributed across thousands of variants rather than a few high-penetrance loci, consistent with complex polygenic inheritance (pqac-00000006) |
| SNP-based heritability | Genome-wide | Common-variant heritability estimate | GWAS | h²SNP 6.7% (SE 0.3%) overall assuming 1% prevalence; subgroup estimates higher in clinically ascertained samples; earlier published estimates ranged ~8.5% to 16%, with older reports up to 28–37% depending on design/assumptions (pqac-00000003, pqac-00000006) | Supports measurable but incomplete capture of total OCD heritability by common SNPs; twin-based heritability remains higher than SNP-based estimates (pqac-00000003) |
| Twin/family heritability | Genome-wide | Familial genetic contribution | Family/twin studies summarized in review | Adults ~27–47%; children ~45–65% (pqac-00000003); broader review notes genetic contribution ~35–50% (pqac-00000005) | Higher heritability in pediatric-onset OCD supports stronger genetic loading in early-onset presentations (pqac-00000003, pqac-00000011) |
| WDR6 | 2q33 | WD repeat domain 6; prioritized likely causal effector gene | GWAS + gene prioritization + TWAS-COLOC/SMR-HEIDI | Among 25 genes prioritized as most likely causal; implicated by multiple methods (pqac-00000003, pqac-00000010) | One of only two genes prioritized by both TWAS-COLOC and SMR-HEIDI filters, strengthening causal inference beyond positional association alone (pqac-00000010) |
| DALRD3 | 2q33 | DALR anticodon binding domain-containing 3; prioritized likely causal effector gene | GWAS + gene prioritization + TWAS-COLOC/SMR-HEIDI | Among 25 genes prioritized as most likely causal; implicated by multiple methods (pqac-00000003, pqac-00000010) | Along with WDR6, one of the strongest cross-method priority genes, supported by convergent colocalization/causality filters (pqac-00000010) |
| CTNND1 | 6p22 | Catenin delta-1; adhesion/synaptic-related gene, prioritized candidate | GWAS + TWAS + PWAS + colocalization | CTNND1 protein downregulation in human dlPFC associated with OCD risk: Z = -4.49, P = 7.11×10⁻⁶; TWAS in prefrontal cortex: Z = -6.86, P = 6.90×10⁻¹² (pqac-00000010) | Especially notable because it was implicated by three orthogonal approaches (mBAT-combo, TWAS, PWAS) and also showed evidence for colocalization, making it one of the most biologically convergent OCD genes (pqac-00000010) |
| MHC region / 6p21.33 locus | 6p21.33 | Major histocompatibility complex region; dense immune-related locus | GWAS | Lead SNP rs4990036, P = 1.45×10⁻¹¹; 118 genes within regional window (pqac-00000006) | MHC-region signal suggests possible neuroimmune contribution to OCD biology, although fine-mapping is challenging because of high linkage disequilibrium and gene density (pqac-00000003, pqac-00000006) |
| rs78587207 locus | 11q12.1 | Genome-wide significant lead SNP region | GWAS | P = 5.28×10⁻¹² (pqac-00000006) | One of the strongest individual loci in the meta-analysis; also overlaps signals seen in schizophrenia, well-being, neuroticism, and educational attainment databases (pqac-00000006) |
| rs13262595 locus | 8q24.3 | Genome-wide significant lead SNP region | GWAS | P = 1.31×10⁻¹¹ (pqac-00000006) | Strong association signal with cross-trait overlap including schizophrenia, neuroticism, and educational attainment, highlighting pleiotropy (pqac-00000006) |
| rs10877425 locus | 12q14.1 | Genome-wide significant lead SNP region | GWAS | P = 1.62×10⁻¹¹ (pqac-00000006) | High-confidence OCD locus without a highlighted nearby gene in the summary table, illustrating that some strong associations remain functionally unresolved (pqac-00000006) |
| rs7626445 locus | 3p21.31 | Genome-wide significant lead SNP region | GWAS | P = 1.74×10⁻¹¹ (pqac-00000006) | Associated region overlaps neuroticism, smoking, blood cell count, and height traits, again indicating polygenic pleiotropy (pqac-00000006) |
| rs2564930 locus | 3p21.1 | Genome-wide significant lead SNP region | GWAS | P = 3.41×10⁻¹¹ (pqac-00000006) | Strong signal in a region also linked to schizophrenia, neuroticism, blood cell count, and BMI (pqac-00000006) |
| rs4702 locus | 15q26.1 | Genome-wide significant lead SNP region | GWAS | P = 9.07×10⁻¹⁰ (pqac-00000006) | Notable because the same locus shows associations with bipolar disorder, major depressive disorder, and risk-taking behavior, consistent with shared psychiatric liability (pqac-00000006) |
| Gene-based discovery summary | Genome-wide | Aggregated gene-level prioritization from multiple methods | mBAT-combo / TWAS / SMR / PWAS / PsyOPS | 251 genes significant in at least one gene-based method; 48 genes implicated by ≥2 methods; 25 genes passed additional causal-support filters (pqac-00000006, pqac-00000010) | Multi-method integration greatly narrowed the candidate list from hundreds of genes to a smaller set of more plausible effector genes for functional follow-up (pqac-00000006, pqac-00000010) |
| Tissue enrichment | Brain tissues | Regional expression enrichment of OCD-associated genes | MAGMA / LDSC | Enrichment seen in anterior cingulate cortex, frontal cortex, cortex, nucleus accumbens, hippocampus, caudate, putamen, hypothalamus, substantia nigra, cerebellum and related brain tissues (pqac-00000010) | Supports a brain-circuit model centered on cortico-striatal and limbic systems rather than a diffuse whole-body signal (pqac-00000010, pqac-00000008) |
| Cell-type enrichment | Hippocampus, cortex, striatum | Neuronal cell classes implicated by genetic risk | Single-cell enrichment from GWAS signals | Significant enrichment in excitatory neurons in hippocampus/cortex and D1/D2 dopamine receptor-containing medium spiny neurons in striatum (pqac-00000003, pqac-00000010) | Provides cell-type specificity linking OCD genetic risk to excitatory cortical/hippocampal neurons and striatal medium spiny neurons, consistent with CSTC circuit models (pqac-00000003, pqac-00000010, pqac-00000008) |
| Cross-trait genetic correlations | Genome-wide | Shared inherited liability with other disorders/traits | GWAS genetic correlation | OCD shared genetic risk with 65 of 112 phenotypes; especially anxiety, depression, anorexia nervosa, Tourette syndrome; negative associations with inflammatory bowel diseases, educational attainment, and BMI (pqac-00000003) | Reinforces that OCD genetics overlap substantially with other psychiatric phenotypes while also showing inverse relationships with some immune/metabolic traits (pqac-00000003) |
| Ascertainment and heterogeneity analyses | Genome-wide | Robustness of results across cohorts | GWAS / GenomicSEM | No statistically significant heterogeneity across the 30 lead loci by Cochran’s Q; moderate-to-high genetic correlations across ascertainment subgroups (pqac-00000006) | Suggests that major loci are broadly consistent across different OCD cohorts, even though ascertainment strategy influences genome-wide architecture to some extent (pqac-00000006) |


*Table: This table summarizes the major genetic findings for obsessive-compulsive disorder from recent large-scale GWAS and gene-prioritization analyses. It highlights the most important loci, candidate genes, heritability estimates, and polygenic architecture features that are most useful for a disease knowledge base.*