Investigation of gene-environment interactions in relation to tic severity.

Mohamed Abdulkadir, Dongmei Yu, Lisa Osiecki, Robert A King, Thomas V Fernandez, Lawrence W Brown, Keun-Ah Cheon, Barbara J Coffey, Blanca Garcia-Delgar, Donald L Gilbert, Dorothy E Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Alexander Münchau, Kerstin J Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Frank Visscher, Samuel H Zinner, Carol A Mathews, Jeremiah M Scharf, Jay A Tischfield, Gary A Heiman, Andrea Dietrich, Pieter J Hoekstra

Journal: Journal of neural transmission (Vienna, Austria : 1996) 2021;128(11):1757-1765

PMID: 34389898

Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

© 2021. The Author(s).

Address: Department of Child and Adolescent Psychiatry, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. [email protected].; Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA. [email protected].; Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.; Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.; Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.; Yale Child Study Center, Yale University School of Medicine, New Haven, CT, 06510, USA.; Pediatric Neuropsychiatry Program, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Yonsei University College of Medicine, Severance Hospital, Seoul, 120-752, South Korea.; Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.; University of Miami Miller School of Medicine, Miami, FL, 33146, USA.; Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, Spain.; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Child and Adolescent Mental Health Center, Mental Health Services, Capital Region of Denmark and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.; Evelina London Children's Hospital GSTT, Kings Health Partners AHSC, London, UK.; Psychological Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.; Department of Psychiatry, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi, 14068, South Korea.; Academic Center for Child and Adolescent Psychiatry De Bascule, 1105 AZ, Amsterdam, The Netherlands.; Family Health Centers at NYU Langone, Brooklyn, NY, 11220, USA.; Department of Psychiatry, Yonsei Bom Clinic, Seoul, 03330, South Korea.; University of California San Francisco Medical Center, San Francisco, CA, 94143, USA.; Korea Institute for Children's Social Development, Seoul, South Korea.; Yonsei-Nuri Mental Health Clinic, Seoul, 08005, South Korea.; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa, IA, 52242, USA.; Sección de Neuropediatría, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.; Yulius Academy, Yulius Mental Health Organization, 3311 JG, Dordrecht, The Netherlands.; Unidad de Trastornos del MovimientoInstituto de Biomedicina de Sevilla (IBiS). Hospital Universitario Virgen del Rocío/CSICUniversidad de Sevilla, Seville, Spain.; Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIPABS) and Centro de Investigacion en Red de Salud Mental (CIBERSAM), Barcelona, Spain.; Institute of Systems of Motor Science, University of Lübeck, 23562, Lübeck, Germany.; Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany.; Yonsei University Severance Hospital, Seoul, 03722, South Korea.; Department of Psychiatry, National Health Insurance Service Ilsan Hospital, Goyang, Gyeonggi, 10444, South Korea.; Admiraal De Ruyter Ziekenhuis, Department of Neurology, Goes, The Netherlands.; Department of Pediatrics, Division of Developmental Medicine, University of Washington School of Medicine, 1925 NE Pacific Street, Box 356524, Seattle, WA, 98195, USA.; Department of Psychiatry, Center for OCD, Anxiety and Related Disorders, and Genetics Institute, University of Florida College of Medicine, Gainesville, FL, 32611, USA.; Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.; Department of Child and Adolescent Psychiatry, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
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