Poster Presentation GENEMAPPERS 2026

Genomic data linkage identifies candidate genetic factors associated with congenital heart disease surgery outcomes (#97)

Emma Rath 1 , Gillian Blue 2 , Eddie Ip 1 , Debjani Das 1 , Michael Troup 1 , Edwin Kirk 3 , Samantha Lain 1 , Bridget O'Malley 3 , Gary Sholler 3 , Gavin Chapman 1 , Natasha Nassar 4 , David Winlaw 5 , Sally Dunwoodie 1 , Eleni Giannoulatou 1
  1. Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
  2. Heart Centre for Children, Sydney, NSW, Australia
  3. NSW Health, Sydney, NSW, Australia
  4. University of Sydney, Sydney, NSW, Australia
  5. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA

Aim

Outcomes after paediatric congenital heart disease (CHD) surgery vary widely even for the same lesion and repair. The aim of this Synergy study is to identify genetic hallmarks of unfavourable postoperative outcomes in CHD.

Methods

Children with CHD were classified as having unfavourable (n=267) or favourable (n=222) cardiovascular outcomes using our discovery cohort of NSW linked health data and underwent whole-exome sequencing. We performed rare-variant burden testing across 20,523 genes and 16,624 biological pathways, comparing unfavourable versus favourable groups. Significant signals were then interrogated in an independent Genomics England replication cohort (unfavourable n=232; favourable n=252) to assess replication.

Results

Unfavourable-outcome patients showed a higher burden of rare, deleterious variants in the bile acid gene SCL10A2, in a clotting factor XIII pathway, and in a TP53 cell cycle pathway. Intriguingly, favourable-outcome patients showed a higher burden of rare, deleterious variants in the cilia gene DNHD1.

Conclusion

Postoperative outcomes after CHD surgery are affected by genetic defects involved in bleeding and clotting, factors that are exacerbated by the cardiopulmonary bypass required for cardiac surgery. These findings require further validation, and suggest that actions will be possible to mitigate unfavourable outcomes resulting from defects in clotting-associated genes. Further genes also impact outcomes, and do not appear to be related to causal genetics of the underlying CHD disease.