Did whole genome sequencing find rare gene variants in obsessive-compulsive disorder families?
Whole genome sequencing (WGS) and exome sequencing studies have identified rare gene variants in families with obsessive-compulsive disorder (OCD). These rare variants may contribute to the genetic risk for OCD, especially in families where multiple members are affected. While many genetic factors remain unknown, these findings help point to specific genes and biological pathways involved.
What the research says
A study using whole genome sequencing in two large OCD families found rare variants in three genes: NPY5R, DLGAP1, and MAPK8IP3 3. In one family, a harmful variant in NPY5R was carried by most affected members; this gene is active in the brain and has been linked to panic disorder and internet addiction 3. In the other family, a large deletion in DLGAP1 and a variant in MAPK8IP3 perfectly matched the OCD pattern in one branch of the family 3. Both DLGAP1 and MAPK8IP3 have been previously linked to OCD and autism, and they interact with proteins found in a Tourette syndrome study 3.
Larger exome sequencing studies (which focus on the protein-coding parts of the genome) have also found rare variants in OCD. One study of over 1,300 OCD cases found an excess of rare damaging variants in the SLITRK5 gene and in genes that are intolerant to loss-of-function mutations 6. Another study of 20 OCD families found a higher rate of new (de novo) mutations compared to the general population, with mutations in genes involved in immune and neurodevelopmental pathways 7.
A separate study on children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), which includes OCD symptoms, used exome and whole genome sequencing and found ultra-rare variants in 11 genes, including SHANK3, SYNGAP1, and GRIN2A, which are involved in immune responses and neuronal synapses 8. These findings suggest that rare genetic variants in OCD and related conditions may affect similar biological pathways.
What to ask your doctor
- Could genetic testing help explain my or my family's OCD?
- What do we know about the specific genes NPY5R, DLGAP1, and MAPK8IP3 in OCD?
- Are there any ongoing studies on genetics of OCD that I might join?
- How do rare genetic variants influence treatment options for OCD?
- Should I consider genetic counseling for my family?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.