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 expression quantitative trait locus (eQTL) mapping was performed with transcriptome-wide association study (TWAS)20, using PsychENCODE gene expression weights21, and summary-based Mendelian randomization (SMR)22 using the whole-blood eQTLGen23 and MetaBrain24 datasets. Functional protein QTL mapping was done using a protein-wide association study (PWAS) of human brain protein expression panels25. Finally, we used the psychiatric omnilocus prioritization score (PsyOPS)26, 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 SMR–eQTLGen 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 three 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 (Methods, Supplementary Note 7 and Supplementary Tables 9–14).
