Additionally, in 2011, we initiated a GWAS for pediatric venous thrombosis. Single-point and haplotype association was performed using the transmission disequilibrium test (TDT) as implemented in PLINK and FBAT, respectively, and corrected for multiple testing. Additionally, associations were adjusted for age, sex, and, in a subsequent analysis, factor V Leiden, an established risk factor for venous thrombosis in children and adults. Four SNPs exceeded the threshold for genome-wide significance and are presumed to be true associations. Of these, two SNPs are located in a genomic region on chromosome 6q13 containing the gene for beta-1,3-glucoronyltransferase 2 (B3GAT2), a member of the human natural killer 1 (HNK1) carbohydrate pathway. The corresponding haplotype association test resulted in a highly significant P-value (p<10-6), further underscoring the underlying association. Interestingly, B3GAT2 was recently also associated with hemoglobin levels in an African-American population with sickle cell anemia, strongly underscoring the role of this gene in both hematopoiesis and coagulation. Furthermore, sickle cell anemia is a prime example of diseases in which selective pressure exerts effects on the genome and comorbidities, as carriers of the sickle cell mutation in the hemoglobin gene are resistant to malaria. This means that from an evolutionary perspective, sickle cell anemia is accepted as a less severe disease than malaria, and the corresponding mutation has spread over the millennia as a protective allele, at least in heterozygous form, in malaria-endemic areas. Our studies on the role of selective pressure on the B3GAT2 locus confirm this phenomenon for this locus as well, further supporting our hypothesis of selection as a cofactor in the development of complex diseases. Encouragingly, we were able to replicate the observed association of the B3GAT2 SNPs in an independent cohort of young adults with venous thrombosis and adequate controls from the POPGEN cohort (P<0.02) and made the requested revisions to the manuscript submitted in 2012. The revised manuscript has currently been resubmitted for publication. The studies in 2013 focused on evaluating the results from the sequencing of the loci implicated by the GWAS in 48 children, conducted in 2012, analogous to our approach for pediatric stroke. The rare variants identified by bioinformatic analysis of the NGS results were verified by capillary sequencing and subsequently genotyped across the entire cohort using TaqMan genotyping. Here, too, significant progress was made, with the identification of coding mutations in some of the implicated genes.which were then also genotyped in the entire cohort and are significantly associated with the occurrence of venous thrombosis (P<10-6). The final work, genotyping of remaining candidate SNPs from the NGS and bioinformatics analysis, is currently underway and will be submitted for publication by summer 2014. Furthermore, a related application for research funding from the DFG is currently nearing completion and is expected to be submitted in the coming weeks.