Abstract
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.
Original language | English |
---|---|
Article number | 91 |
Journal | Translational Psychiatry |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jun 2021 |
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In: Translational Psychiatry, Vol. 11, No. 1, 91, 01.06.2021.
Research output: Contribution to journal › Article › Academic › peer-review
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 - Jenike, Michael
AU - Keenan, Clare L.
AU - Kennedy, James L.
AU - Khramtsova, Ekaterina A.
AU - Knowles, James A.
AU - Krasnow, Janice
AU - Smit, Jan H.
AU - Vulink, Nienke
AU - Posthuma, Danielle
N1 - Funding Information: We thank the families and children that participated in this study and the Ontario Science Centre for their collaboration and support. This study was funded by the Canadian Institutes of Health Research (P.D.A.: MOP-106573; R.J.S.: MOP-93696). P.D.A. is supported by the Alberta Innovates Translational Health Chair in Child and Youth Mental Health. The OCD Collaborative Genetics Association Study (OCGAS) was funded by the following NIMH Grant Numbers: MH071507 (G.N.), MH079489 (D.A.G.), MH079487 (J.M.), MH079488 (A.F.), and MH079494 (J.K.). Y.Y.S. and W.G. were also supported by the Intramural Research Program of the NIMH (MH002930-06). The IOCDF-GC was supported by a grant from the David Judah Foundation (a private, nonindustry-related foundation established by a family affected by OCD), MH079489 (D.L.P.), MH073250 (D.L.P.), S40024 (J.M.S.), MH 085057 (J.M.S.), and MH087748 (C.A.M.). Support for the collection of the data for Philadelphia Neurodevelopment Cohort (PNC) was provided by grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All subjects were recruited through the Center for Applied Genomics at The Children’s Hospital in Philadelphia. The Michigan/Toronto sample was supported by the Ontario Brain Institute – Province of Ontario Neurodevelopmental Disorders (POND) Network (grant number: IDP-PND-2018; awarded to R.J.S., J.C., and P.D.A.) and the National Institutes of Mental Health (MH101493 awarded to GH and PDA; MH085321 awarded to G.H., D.R., and PD.A.). The authors wish to thank Tara Paton, Chao Lu, and Jo-Anne Herbrick of The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada for assistance with genotyping. We gratefully acknowledge all the studies and databases that made GWAS summary data available: ADIPOGen (Adiponectin genetics consortium), C4D (Coronary Artery Disease Genetics Consortium), CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), CKDGen (Chronic Kidney Disease Genetics consortium), dbGAP (database of Genotypes and Phenotypes), DIAGRAM (DIAbetes Genetics Replication And Meta-analysis), ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis), EAGLE (EArly Genetics & Lifecourse Epidemiology Eczema Consortium, excluding 23andMe), EGG (Early Growth Genetics Consortium), GABRIEL (A Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community), GCAN (Genetic Consortium for Anorexia Nervosa), GEFOS (GEnetic Factors for OSteoporosis Consortium), GIANT (Genetic Investigation of ANthropometric Traits), GIS (Genetics of Iron Status consortium), GLGC (Global Lipids Genetics Consortium), GPC (Genetics of Personality Consortium), GUGC (Global Urate and Gout consortium), HaemGen (haemotological and platelet traits genetics consortium), HRgene (Heart Rate consortium), IIBDGC (International Inflammatory Bowel Disease Genetics Consortium), ILCCO (International Lung Cancer Consortium), IMSGC (International Multiple Sclerosis Genetic Consortium), MAGIC (Meta-Analyses of Glucose and Insulin-related traits Consortium), MESA (Multi-Ethnic Study of Atherosclerosis), PGC (Psychiatric Genomics Consortium), Project MinE consortium, ReproGen (Reproductive Genetics Consortium), SSGAC (Social Science Genetics Association Consortium), TAG (Tobacco and Genetics Consortium), TRICL (Transdisciplinary Research in Cancer of the Lung consortium), and UK Biobank. We gratefully acknowledge the contributions of Alkes Price (the systemic lupus erythematosus GWAS and primary biliary cirrhosis GWAS) and Johannes Kettunen (lipids metabolites GWAS). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
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 - https://doi.org/10.1038/s41398-020-01121-9
DO - https://doi.org/10.1038/s41398-020-01121-9
M3 - Article
C2 - 33531474
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 91
ER -