Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.

Details

Serval ID
serval:BIB_53E970B13A34
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.
Journal
Molecular psychiatry
Author(s)
Halvorsen M., Szatkiewicz J., Mudgal P., Yu D., Nordsletten A.E., Mataix-Cols D., Mathews C.A., Scharf J.M., Mattheisen M., Robertson M.M., McQuillin A., Crowley J.J.
Working group(s)
Psychiatric Genomics Consortium TS/OCD Working Group
Contributor(s)
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.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
15/09/2021
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Pubmed
Web of science
Create date
12/11/2021 14:57
Last modification date
13/11/2021 6:36
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