Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder
Authors: Burton Christie L. , Lemire Mathieu , Xiao Bowei , Corfield Elizabeth C. , Erdman Lauren , Bralten Janita , Poelmans Geert , Yu Dongmei , Shaheen S.-M. , Goodale Tara , Sinopoli Vanessa M. ,   OCD Working Group of the Psychiatric Genomics Consortium, Askland Kathleen D. , Barlassina Cristina , Bienvenu O. Joseph , Black Donald , Bloch Michael , Brentani Helena , Camarena Beatriz , Cappi Carolina , Cath Danielle , Cavallini M. Cristina , Ciullo Valentina , Conti David , Cook Edwin H. , Coric Vladimir , Cullen Bernadette A. , Cusi Danielle , Davis Lea K. , Delorme Richard , Denys Damiaan , Derks Eske , Eapen Valsamma , Edlund Christopher , Falkai Peter , Fyer Abby J. , Geller Daniel A. , Goes Fernando S. , Grabe Hans J. , Grados Marco A. , Greenberg Benjamin D. , Grünblatt Edna , Guo Wei , Hounie Ana G. , Jenike Michael , Keenan Clare L. , Kennedy James L. , Khramtsova Ekaterina A. , Knowles James A. , Krasnow Janice , Lange Cristoph , Lanzagorta Nuria , Leboyer Marion , Liang Kung-Yee , Lochner Christine , Macciardi Fabio , Maher Brion , Mathews Carol A. , Mattheisen Manuel , McCracken James T. , McGregor Nathaniel , McLaughlin Nicole C. R. , Miguel Euripedes c. , Neale Benjamin , Nestadt Gerald , Nestadt Paul S. , Nicolini Humberto , Nurmi Erika L. , Osiecki Lisa , Piacentini John , Pittenger Christopher , Posthuma Danielle , Pulver Ann E. , Rasmussen Steven A. , Rauch Scott , Richter Margaret A. , Riddle Mark A. , Ripke Stephan , Ruhrmann Stephan , Sampaio Aline S. , Samuels Jack F. , Scharf Jeremiah M. , Shugart Yin Yao , Smit Jan H. , Stein Dan J. , Stewart S. Evelyn , Turiel Maurizio , Vallada Homero , Veenstra-VanderWeele Jeremy , Vulink Nienke , Wagner Michael , Walitza Susanne , Wang Ying , Wendland Jens , Zai Gwyneth , Soreni Noam , Hanna Gregory L. , Fitzgerald Kate D. , Rosenberg David , Nestadt Gerald , Paterson Andrew D. , Strug Lisa J. , Schachar Russell J. , Crosbie Jennifer , Arnold Paul D. 
Published: February 2021

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.