| Literature DB >> 33462189 |
Fotis Tsetsos1, Dongmei Yu2,3, Jae Hoon Sul4,5, Alden Y Huang4,5,6, Cornelia Illmann2, Lisa Osiecki2, Sabrina M Darrow7, Matthew E Hirschtritt7, Erica Greenberg8, Kirsten R Muller-Vahl9, Manfred Stuhrmann10, Yves Dion11, Guy A Rouleau12, Harald Aschauer13,14, Mara Stamenkovic13, Monika Schlögelhofer14, Paul Sandor15, Cathy L Barr16, Marco A Grados17, Harvey S Singer17, Markus M Nöthen18, Johannes Hebebrand19, Anke Hinney19, Robert A King20, Thomas V Fernandez20, Csaba Barta21, Zsanett Tarnok22, Peter Nagy22, Christel Depienne23,24, Yulia Worbe24,25,26,27, Andreas Hartmann24,25,26, Cathy L Budman28, Renata Rizzo29, Gholson J Lyon30, William M McMahon31, James R Batterson32, Danielle C Cath33, Irene A Malaty34, Michael S Okun34, Cheston Berlin35, Douglas W Woods36, Paul C Lee37, Joseph Jankovic38, Mary M Robertson39, Donald L Gilbert40, Lawrence W Brown41, Barbara J Coffey42, Andrea Dietrich43, Pieter J Hoekstra43, Samuel Kuperman44, Samuel H Zinner45, Michael Wagner46, James A Knowles47, A Jeremy Willsey48, Jay A Tischfield49, Gary A Heiman49, Nancy J Cox50, Nelson B Freimer4,5, Benjamin M Neale2,3,51, Lea K Davis50, Giovanni Coppola4,5, Carol A Mathews52, Jeremiah M Scharf2,3,53, Peristera Paschou59, Cathy L Barr16, James R Batterson32, Cheston Berlin35, Cathy L Budman28, Danielle C Cath33, Giovanni Coppola4,5, Nancy J Cox50, Sabrina Darrow7, Lea K Davis50, Yves Dion11, Nelson B Freimer4,5, Marco A Grados17, Erica Greenberg8, Matthew E Hirschtritt7, Alden Y Huang4,5,6, Cornelia Illmann2, Robert A King20, Roger Kurlan55, James F Leckman56, Gholson J Lyon30, Irene A Malaty34, Carol A Mathews52, William M McMahon31, Benjamin M Neale2,3,51, Michael S Okun34, Lisa Osiecki2, Mary M Robertson39, Guy A Rouleau12, Paul Sandor15, Jeremiah M Scharf2,3,53, Harvey S Singer17, Jan H Smit57, Jae Hoon Sul4,5, Dongmei Yu2,3, Harald Aschauer Harald Aschauer13,14, Csaba Barta21, Cathy L Budman28, Danielle C Cath33, Christel Depienne23,24, Andreas Hartmann24,25,26, Johannes Hebebrand19, Anastasios Konstantinidis13,58, Carol A Mathews52, Kirsten Müller-Vahl9, Peter Nagy22, Markus M Nöthen18, Peristera Paschou59, Renata Rizzo29, Guy A Rouleau12, Paul Sandor15, Jeremiah M Scharf2,3,53, Monika Schlögelhofer14, Mara Stamenkovic13, Manfred Stuhrmann10, Fotis Tsetsos1, Zsanett Tarnok22, Tomasz Wolanczyk60, Yulia Worbe24,25,26,27, Lawrence Brown41, Keun-Ah Cheon61, Barbara J Coffey42, Andrea Dietrich43, Thomas V Fernandez20, Blanca Garcia-Delgar62, Donald Gilbert40, Dorothy E Grice63, Julie Hagstrøm64, Tammy Hedderly65,66, Gary A Heiman49, Isobel Heyman67,68, Pieter J Hoekstra43, Chaim Huyser69, Young Key Kim70, Young-Shin Kim71, Robert A King20, Yun-Joo Koh72, Sodahm Kook73, Samuel Kuperman44, Bennett L Leventhal71, Marcos Madruga-Garrido74, Pablo Mir75,76, Astrid Morer77,78,79, Alexander Münchau80, Kerstin J Plessen81,82,83, Veit Roessner84, Eun-Young Shin61, Dong-Ho Song61, Jungeun Song85, Jay A Tischfield49, A Jeremy Willsey48, Samuel Zinner45, Harald Aschauer13,14, Cathy L Barr16, Csaba Barta21, James R Batterson32, Cheston Berlin35, Lawrence Brown41, Cathy L Budman28, Danielle C Cath33, Barbara J Coffey42, Giovanni Coppola4,5, Nancy J Cox50, Sabrina Darrow7, Lea K Davis50, Christel Depienne23,24, Andrea Dietrich43, Yves Dion11, Thomas Fernandez20, Nelson B Freimer4,5, Donald Gilbert40, Marco A Grados17, Erica Greenberg8, Andreas Hartmann24,25,26, Johannes Hebebrand19, Gary Heiman49, Matthew E Hirschtritt7, Pieter Hoekstra43, Alden Y Huang4,5,6, Cornelia Illmann2, Joseph Jankovic38, Robert A King20, Samuel Kuperman44, Paul C Lee37, Gholson J Lyon30, Irene A Malaty34, Carol A Mathews52, William M McMahon31, Kirsten Müller-Vahl9, Peter Nagy22, Benjamin M Neale2,3,51, Markus M Nöthen18, Michael S Okun34, Lisa Osiecki2, Peristera Paschou59, Renata Rizzo29, Mary M Robertson39, Guy A Rouleau12, Paul Sandor15, Jeremiah M Scharf2,3,53, Monika Schlögelhofer14, Harvey S Singer17, Mara Stamenkovic13, Manfred Stuhrmann10, Jae Hoon Sul4,5, Zsanett Tarnok22, Jay Tischfield49, Fotis Tsetsos1, A Jeremy Willsey48, Douglas Woods36, Yulia Worbe24,25,26,27, Dongmei Yu2,3, Samuel Zinner45.
Abstract
Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.Entities:
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Year: 2021 PMID： 33462189 PMCID： PMC7814139 DOI： 10.1038/s41398-020-01082-z
Source DB: PubMed Journal: Transl Psychiatry ISSN： 2158-3188 Impact factor: 6.222