TY - JOUR
T1 - Genome-wide association study of pediatric obsessive-compulsive traits
T2 - shared genetic risk between traits and disorder
AU - OCD Working Group of the Psychiatric Genomics Consortium
AU - Burton, Christie L.
AU - Lemire, Mathieu
AU - Xiao, Bowei
AU - Corfield, Elizabeth C.
AU - Erdman, Lauren
AU - Bralten, Janita
AU - Poelmans, Geert
AU - Yu, Dongmei
AU - Shaheen, S. M.
AU - Goodale, Tara
AU - Sinopoli, Vanessa M.
AU - Askland, Kathleen D.
AU - Barlassina, Cristina
AU - Bienvenu, O. Joseph
AU - Black, Donald
AU - Bloch, Michael
AU - Brentani, Helena
AU - Camarena, Beatriz
AU - Cappi, Carolina
AU - Cath, Danielle
AU - Cavallini, M. Cristina
AU - Ciullo, Valentina
AU - Conti, David
AU - Cook, Edwin H.
AU - Coric, Vladimir
AU - Cullen, Bernadette A.
AU - Cusi, Danielle
AU - Davis, Lea K.
AU - Delorme, Richard
AU - Denys, Damiaan
AU - Derks, Eske
AU - Eapen, Valsamma
AU - Edlund, Christopher
AU - Falkai, Peter
AU - Fyer, Abby J.
AU - Geller, Daniel A.
AU - Goes, Fernando S.
AU - Grabe, Hans J.
AU - Grados, Marco A.
AU - Greenberg, Benjamin D.
AU - Grünblatt, Edna
AU - Guo, Wei
AU - Hounie, Ana G.
AU - Maher, Brion
AU - Nestadt, Paul S.
AU - Pulver, Ann E.
AU - Riddle, Mark A.
AU - Samuels, Jack F.
AU - Wang, Ying
AU - Nestadt, Gerald
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100466162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100466162&partnerID=8YFLogxK
U2 - 10.1038/s41398-020-01121-9
DO - 10.1038/s41398-020-01121-9
M3 - Article
C2 - 33531474
AN - SCOPUS:85100466162
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 91
ER -