We prioritized putative risk genes for OCD using six positional and functional QTL gene-based mapping approaches. Positional mapping was performed with mBAT-combo19. Functional eQTL mapping was performed with transcriptome-wide association study (TWAS)20 using PsychENCODE gene expression weights21, and summary-based Mendelian randomization (SMR)22 using whole blood eQTLGen23 and MetaBrain24 datasets. Functional protein QTL (pQTL) mapping was done using a protein-wide association study (PWAS) of human brain protein expression panels25. Finally, we used PsyOPS26, which combines positional mapping with biological annotations, to further prioritize risk genes within genome-wide significant loci. We identified 207 significant genes (Bonferroni correction, P < 2.67 × 10−6) with mBAT-combo, and 24 genes using TWAS (P < 4.76 × 10−6), 14 of which were conditionally independent. The SMReQTLGen analysis identified 39 significant risk genes (P < 4.28 × 10−6), and the SMR-MetaBrain analysis identified 14 risk genes (P < 9.23 × 10−6). The PWAS identified 3 significant genes (P < 3.39 × 10−5), while PsyOPS prioritized 29 genes. In total, 251 genes were significantly associated with OCD through at least one gene-based approach, and 48 were implicated by at least two methods (details in Online Methods, Supplementary Note 7, and Supplementary Tables 9–14).
