Leftsided obstructive heart lesions lesions, (including hypoplastic left heart syndrome, congenital aortic stenosis and congenital aortic coarctation) are congenital heart diseases that require life-saving surgical interventions. The causes of these diseases are unknown, however genetics are thought to play a role in mediating disease risk - with both inherited (familial) and de novo genetic variants being suspected. Nonetheless, studies on the genetic associations with these diseases have been few and far between. This in turn leaves methods such as whole-genome sequencing underutilized in the clinical setting for diagnosing these diseases. From 2014 samples from individuals affected by congenital heart diseases in Sweden have been collected in the Swedish national biobank for congenital heart diseases (Svensk nationell biobank för medfödda hjärtsjukdomar - snab-chd.se). Using samples from the SNAB-CHD biobank from individuals born with congenital aortic coarctation, aortic stenosis, hypoplastic left heart syndrome or other leftsided obstructive heart lesions, we hope to use novel methods of combining cross-diagnosis samples to find novel associations with particular sub-phenotypes of these life threatening diseases. This project will include data from several sources, partly overlapping with the currently ongoing project sens2021603 where only WGS data from a partly overlapping set of individuals is analyzed. From the biobank, 48 saliva samples each from HLHS have been extracted, DNA isolated, and sent to the SNP&SEQ facility in Uppsala for whole genome sequencing using the Illumina TruSeq PCR-free library prep and unique dual indexes, targeting an insert size of 350bp. Paired-end 150bp read length sequencing (30x) is then performed using the NovaSeq 6000 on a S4 flowcell. At the sequencing facility, alignment, variant discovery and variant annotation is implemented using nf-core Sarek. At this time, five additional samples from WGS of individuals with a familial form of other leftsided obstructive heart lesions are already available, and a handful of more samples could become available to us. Bioinformatics support has been obtained via the National Bioinformatics Support (NBIS) for the WGS data analysis. As most of the data is already available, we believe we will manage the necessary analysis for this project within one year.