TY - JOUR
T1 - Pharmacogenetics of obsessive-compulsive disorder
T2 - Investigations of intragenic and regulatory region genetic variations
AU - Zai, Gwyneth
AU - Zai, Clement C.
AU - Gonçalves, Vanessa F.
AU - Wigg, Karen
AU - Lochner, Christine
AU - Stein, Dan J.
AU - Mathews, Carol A.
AU - Kennedy, James L.
AU - Richter, Margaret A.
N1 - Publisher Copyright:
© 2024
PY - 2025/4/2
Y1 - 2025/4/2
N2 - Few pharmacogenetic studies on the use of genetic variations to predict antidepressant response in obsessive-compulsive disorder (OCD) have been published. This study expanded on the limited literature on single nucleotide polymorphisms (SNPs) across previously identified putative susceptibility genes for OCD, by incorporating known functional regulatory elements for all genes of interest. We investigated 17 SNPs in 12 genes implicated in OCD risk in 206 European ancestry OCD patients with selective serotonin reuptake inhibitor (SSRI) antidepressant response data, examining functional polymorphisms in remote regulatory regions. No association was observed between any regulatory region markers tested and drug response. We observed nominally significant associations between SNPs within the serotonin 1B receptor (5HT1B; SNP rs1778258), SLIT and NTRK-like family member 5 (SLITRK5; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (FAIM2; SNP rs706795), with response to any SSRI, which did not survive multiple comparisons. This study supports a potential role for a number of OCD-associated risk genes in response to antidepressant treatment, warranting further investigation.
AB - Few pharmacogenetic studies on the use of genetic variations to predict antidepressant response in obsessive-compulsive disorder (OCD) have been published. This study expanded on the limited literature on single nucleotide polymorphisms (SNPs) across previously identified putative susceptibility genes for OCD, by incorporating known functional regulatory elements for all genes of interest. We investigated 17 SNPs in 12 genes implicated in OCD risk in 206 European ancestry OCD patients with selective serotonin reuptake inhibitor (SSRI) antidepressant response data, examining functional polymorphisms in remote regulatory regions. No association was observed between any regulatory region markers tested and drug response. We observed nominally significant associations between SNPs within the serotonin 1B receptor (5HT1B; SNP rs1778258), SLIT and NTRK-like family member 5 (SLITRK5; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (FAIM2; SNP rs706795), with response to any SSRI, which did not survive multiple comparisons. This study supports a potential role for a number of OCD-associated risk genes in response to antidepressant treatment, warranting further investigation.
KW - Antidepressant/drug/treatment response
KW - Obsessive-compulsive disorder (OCD)
KW - Pharmacogenetics
KW - Regulatory regions
UR - http://www.scopus.com/inward/record.url?scp=86000447301&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2025.111315
DO - 10.1016/j.pnpbp.2025.111315
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C2 - 40054571
AN - SCOPUS:86000447301
SN - 0278-5846
VL - 138
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 111315
ER -