Genome-wide association study of Tourette's syndrome

Area of Science:

• Neurogenetics
• Psychiatric Genetics
• Human Genetics

Background:

• Tourette's syndrome (TS) is a neurodevelopmental disorder with high familial recurrence, suggesting a complex genetic basis.
• Identifying specific TS susceptibility genes has been challenging despite its genetic heritability.
• Previous genetic studies have not fully elucidated the genetic architecture of TS.

Purpose of the Study:

• To conduct the first genome-wide association study (GWAS) for Tourette's syndrome (TS).
• To identify common genetic variants associated with TS in diverse European ancestry populations.
• To lay the groundwork for future large-scale genetic studies of TS.

Main Methods:

• Genome-wide association study (GWAS) meta-analysis of 1285 TS cases and 4964 controls of European ancestry.
• Inclusion of population isolates (Ashkenazi Jews, French Canadians) to enhance power.
• Secondary analysis incorporating Latin American population isolates (Costa Rica, Colombia) for a combined sample of 1496 cases and 5249 controls.

Main Results:

• No single genetic marker reached the genome-wide significance threshold (P<5 × 10(-8)).
• The top association signal in European ancestry samples was rs7868992 on chromosome 9q32 within the COL27A1 gene (P=1.85 × 10(-6)).
• This top signal (rs7868992) was also the most significant in the combined European and Latin American sample (P=3.6 × 10(-7)).

Conclusions:

• This GWAS provides foundational data for identifying common TS susceptibility variants in larger cohorts.
• The study highlights a potential region on chromosome 9 (COL27A1) for further investigation in TS genetics.
• Further research with larger sample sizes is necessary to fully understand the genetic architecture of Tourette's syndrome.