TY  - JOUR
AB  - 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 family 'ADAMTS2' (rs469568, p = 8x10-6) and 'ADAMTS12' (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 in 'ADAMTS2' and six in 'ADAMTS12' potentially influencing the respective protein function. These variants were genotyped within a cohort of 270 affected offspring trios, association analysis revealed the 'ADAMTS12' variant 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 of 'ADAMTS12' detected a significantly associated haplotype comprising the originally identified GWAS variant. Several ADAMTS genes such as 'ADAMTS13' are involved in thromboembolic disease process. Here, we provide further evidence for 'ADAMTS12' to likely play a role in pediatric stroke. Further functional studies are warranted to assess the functional role of ADAMTS12 in the pathogenesis of stroke.
AU  - Witten, Anika
AU  - Rühle, Frank
AU  - de Witt, Marlous
AU  - Barysenka, Andrei
AU  - Stach, Michael
AU  - Junker, Ralf
AU  - Nowak-Göttl, Ulrike
AU  - Stoll, Monika
DA  - 2020-08-20
DO  - 10.17879/13059492781
KW  - Pediatrics
KW  - Haplotypes
KW  - Stroke
KW  - Genome-wide association studies
KW  - Single nucleotide polymorphisms
KW  - Genotyping
KW  - Alleles
KW  - Venous thromboembolism
LA  - eng
N1  - PLoS ONE 15 (2020) 8, e0237928, 1-10
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2020-08-20
TI  - 'ADAMTS12', a new candidate gene for pediatric stroke
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-93029512848
Y2  - 2024-11-24T21:07:42
ER  -