ADAMTS12, a new candidate gene for pediatric stroke

Area of Science:

• Genetics
• Pediatric Neurology
• Thrombosis

Background:

• Genome-wide association studies (GWAS) identified ADAMTS2 and ADAMTS12 as candidate genes for pediatric stroke.
• Further investigation is needed to clarify the role of these genes in stroke pathogenesis.

Purpose of the Study:

• To investigate the role of ADAMTS2 and ADAMTS12 in pediatric stroke.
• To identify specific variants within these genes associated with the condition.

Main Methods:

• Targeted resequencing of ADAMTS2 and ADAMTS12 in pediatric stroke cases.
• Genotyping of identified non-synonymous variants in a large cohort of pediatric stroke trios.
• Association analysis and haplotype analysis.
• Validation in a pediatric venous thromboembolism (VTE) cohort.

Main Results:

• Eight non-synonymous single nucleotide polymorphisms (SNPs) in ADAMTS2 and six in ADAMTS12 were identified.
• The ADAMTS12 variant rs77581578 was significantly under-transmitted in pediatric stroke patients.
• This finding was validated in a pediatric VTE cohort.
• A significantly associated ADAMTS12 haplotype, including a previously identified GWAS variant, was detected.

Conclusions:

• ADAMTS12 is implicated as a potential contributor to pediatric stroke.
• The study provides evidence supporting a role for ADAMTS12 in the pathogenesis of pediatric stroke.
• Further functional studies are recommended to elucidate the precise mechanisms.