ADAMTS12, a new candidate gene for pediatric stroke

Anika Witten, Frank Ruehle, Marlous de Witt, Andrei Barysenka, Michael Stach, Ralf Junker, Ulrike Nowak-Goettl, Monika Stoll*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)


We recently reported a family-based genome wide association study (GWAS) for pediatric stroke pointing our attention to two significantly associated genes of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene familyADAMTS2(rs469568,p= 8x10(-6)) andADAMTS12(rs1364044,p= 2.9x10(-6)). To further investigate these candidate genes, we applied a targeted resequencing approach on 48 discordant sib-pairs for pediatric stroke followed by genotyping of the detected non-synonymous variants in the full cohort of 270 offspring trios and subsequent fine mapping analysis. We identified eight non-synonymous SNPs inADAMTS2and six inADAMTS12potentially influencing the respective protein function. These variants were genotyped within a cohort of 270 affected offspring trios, association analysis revealed theADAMTS12variant rs77581578 to be significantly under-transmitted (p= 6.26x10(-3)) to pediatric stroke patients. The finding was validated in a pediatric venous thromboembolism (VTE) cohort of 189 affected trios. Subsequent haplotype analysis ofADAMTS12detected a significantly associated haplotype comprising the originally identified GWAS variant. Several ADAMTS genes such asADAMTS13are involved in thromboembolic disease process. Here, we provide further evidence forADAMTS12to likely play a role in pediatric stroke. Further functional studies are warranted to assess the functional role of ADAMTS12 in the pathogenesis of stroke.

Original languageEnglish
Article number0237928
Number of pages10
Issue number8
Publication statusPublished - 20 Aug 2020


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