UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Halvorsen, M; Szatkiewicz, J; Mudgal, P; Yu, D; Nordsletten, AE; Mataix-Cols, D; Mathews, CA; ... Crowley, JJ; + view all (2021) Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree. Molecular Psychiatry , 26 pp. 7522-7529. 10.1038/s41380-021-01277-w. Green open access

[thumbnail of Article]
Preview
Text (Article)
McQuillin_Tourette_pedigree_manuscript.pdf - Accepted Version

Download (234kB) | Preview
[thumbnail of Supplementary Information]
Preview
Text (Supplementary Information)
McQuillin_Supplemental_Figures.pdf - Accepted Version

Download (800kB) | Preview
[thumbnail of Tables] Spreadsheet (Tables)
Supplemental_Tables[1].xlsx - Accepted Version

Download (3MB)
[thumbnail of Figure 1]
Preview
Text (Figure 1)
McQuillin_Figure_1.pdf - Accepted Version

Download (73kB) | Preview
[thumbnail of Figure 2]
Preview
Text (Figure 2)
McQuillin_Figure_2.pdf - Accepted Version

Download (1MB) | Preview
[thumbnail of Figure 3]
Preview
Text (Figure 3)
McQuillin_Figure_3.pdf - Accepted Version

Download (585kB) | Preview

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.

Type: Article
Title: Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41380-021-01277-w
Publisher version: https://doi.org/10.1038/s41380-021-01277-w
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Genetics, Molecular biology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10136751
Downloads since deposit
27Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item