Titre
Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Halvorsen, M.
Auteure/Auteur
Szatkiewicz, J.
Auteure/Auteur
Mudgal, P.
Auteure/Auteur
Yu, D.
Auteure/Auteur
Nordsletten, A.E.
Auteure/Auteur
Mataix-Cols, D.
Auteure/Auteur
Mathews, C.A.
Auteure/Auteur
Scharf, J.M.
Auteure/Auteur
Mattheisen, M.
Auteure/Auteur
Robertson, M.M.
Auteure/Auteur
McQuillin, A.
Auteure/Auteur
Crowley, J.J.
Auteure/Auteur
Contributrices/contributeurs
Aschauer, H.
Atzmon, G.
Barr, C.
Barta, C.
Barzilai, N.
Batterson, J.
Berlin, C.
Bodmer, B.
Bohnenpoll, J.
Brown, L.
Bruun, R.
Buckner, R.
Budman, C.
Cath, D.
Cheon, K.A.
Chouinard, S.
Coffey, B.
Coppola, G.
Cox, N.
Crowley, J.
Darrow, S.
Davis, L.
Depienne, C.
Dietrich, A.
Dion, Y.
Elzerman, L.
Fernandez, T.
Freimer, N.
Fremer, C.
Fründt, O.
Garcia-Delgar, B.
Gilbert, D.
Grados, M.
Greenberg, E.
Grice, D.
Hagstrøm, J.
Halvorsen, M.
Hartmann, A.
Hebebrand, J.
Hedderly, T.
Heiman, G.
Heyman, I.
Hinney, A.
Hirschtritt, M.
Hoekstra, P.
Hong, H.
Huang, A.
Huyser, C.
Ibanez-Gomez, L.
Illmann, C.
Jankovic, J.
Kim, Y.
Kim, Y.S.
King, R.
Knowles, J.
Koh, Y.J.
Konstantinidis, A.
Kook, S.
Kuperman, S.
Kurlan, R.
Leckman, J.
Lee, P.
Leventhal, B.
Ludolph, A.
Luðvigsson, P.
Lyon, G.
Madruga-Garrido, M.
Malaty, I.
Maras, A.
Mataix-Cols, D.
Mathews, C.
Mattheisen, M.
McMahon, W.
McQuillin, A.
Mir, P.
Moessner, R.
Morer, A.
Mudgal, P.
Mueller-Vahl, K.
Murphy, T.
Münchau, A.
Nagy, P.
Nawaz, M.
Neale, B.
Nordsletten, A.
Nöthen, M.
Okun, M.
Ophoff, R.
Osiecki, L.
Paschou, P.
Pato, C.
Pato, M.
Pauls, D.
Plessen, K.
Posthuma, D.
Richer, P.
Rizzo, R.
Robertson, M.
Roessner, V.
Roffman, J.
Rouleau, G.
Sandor, P.
Sæmundsen, E.
Scharf, J.
Schlögelhofer, M.
Shin, E.Y.
Singer, H.
Smit, J.
Smoller, J.
Song, D.H.
Song, J.
Stamenkovic, M.
State, M.
Stefansson, H.
Stefansson, K.
Stuhrmann, M.
Sul, J.
Sæmundsen, E.
Szatkiewicz, J.
Tarnok, Z.
Thorarensen, Ó.
Tischfield, J.
Tsetsos, F.
Tübing, J.
Visscher, F.
Wagner, M.
Wanderer, S.
Wang, S.
Willsey, J.
Wolanczyk, T.
Woods, D.
Woods, M.
Worbe, Y.
Yu, D.
Zelaya, I.
Zinner, S.
Groupes de travail
Psychiatric Genomics Consortium TS/OCD Working Group
Liens vers les personnes
Liens vers les unités
ISSN
1476-5578
Statut éditorial
Publié
Date de publication
2021-12
Volume
26
Numéro
12
Première page
7522
Dernière page/numéro d’article
7529
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as "cases" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.
PID Serval
serval:BIB_53E970B13A34
PMID
Date de création
2021-11-12T13:57:05.328Z
Date de création dans IRIS
2025-05-20T20:20:41Z
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Nom
34526668_BIB_53E970B13A34.pdf
Version du manuscrit
postprint
Taille
768.62 KB
Format
Adobe PDF
PID Serval
serval:BIB_53E970B13A34.P001
URN
urn:nbn:ch:serval-BIB_53E970B13A340
Somme de contrôle
(MD5):d52c26c2146f394dfa259fb66d1aac0f