Produção Nacional
Revisado por pares
Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder
2021; Springer Nature; Volume: 11; Issue: 1 Linguagem: Inglês
10.1038/s41398-020-01121-9
ISSN2158-3188
AutoresChristie L. Burton, Mathieu Lemire, Bowei Xiao, Elizabeth C. Corfield, Lauren Erdman, Janita Bralten, Geert Poelmans, Dongmei Yu, S.‐M. Shaheen, Tara Goodale, Vanessa M. Sinopoli, Kathleen D. Askland, Cristina Barlassina, O. Joseph Bienvenu, Donald W. Black, Michael H. Bloch, Helena Brentani, Beatríz Camarena, Carolina Cappi, Daniëlle C. Cath, Maria Cristina Cavallini, Valentina Ciullo, David V. Conti, Edwin H. Cook, Vladimir Coric, Bernadette Cullen, Daniele Cusi, Lea K. Davis, Richard Delorme, Damiaan Denys, Eske M. Derks, Valsamma Eapen, Christopher K. Edlund, Peter Falkai, Abby J. Fyer, Daniel Geller, Fernando S. Goes, Hans J. Grabe, Marco A. Grados, Benjamin D. Greenberg, Edna Grünblatt, Wei Guo, Ana Gabriela Hounie, Michael A. Jenike, Clare L. Keenan, James L. Kennedy, Ekaterina Khramtsova, James A. Knowles, Janice Krasnow, Cristoph Lange, Nuria Lanzagorta, Marion Leboyer, Kung‐Yee Liang, Christine Löchner, Fabìo Macciardi, Brion S. Maher, Carol A. Mathews, Manuel Mattheisen, James T. McCracken, Nathaniel W. McGregor, Nicole McLaughlin, Eurípedes C. Miguel, Benjamin M. Neale, Gerald Nestadt, Paul S. Nestadt, Humberto Nicolini, Erika L. Nurmi, Lisa Osiecki, John Piacentini, Christopher Pittenger, Daniëlle Posthuma, Ann E. Pulver, Steven A. Rasmussen, Scott L. Rauch, Margaret A. Richter, Mark A. Riddle, Stephan Ripke, Stephan Ruhrmann, Aline S. Sampaio, Jack Samuels, Jeremiah M. Scharf, Yin Yao Shugart, Jan Smit, Dan J. Stein, S. Evelyn Stewart, Maurizio Turiel, Homero Vallada, Jeremy Veenstra‐VanderWeele, Nienke Vulink, Michael Wagner, Susanne Walitza, Ying Wang, Jens R. Wendland, Gwyneth Zai, Noam Soreni, Gregory L. Hanna, Kate D. Fitzgerald, David Rosenberg, Gerald Nestadt, Andrew D. Paterson, Lisa J. Strug, Russell Schachar, Jennifer Crosbie, Paul Arnold,
Tópico(s)Child Nutrition and Feeding Issues
ResumoUsing 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.
Referência(s)