American Society of Human Genetics 2024 Posters

Researchers at Helix unveiled new clinical research presentations that continue to underscore the power of genomic insights at the ASHG 2024 Annual Meeting from November 5-9, 2024, in Denver, Colorado.

Presentations included the latest findings from Helix and collaborators, detailing discovery of rare coding variants using a sliding window technique, the impact of foregoing routine pharmacogenetic testing on major adverse events, genetics of Crohn's Disease and more.

Adverse events increased by 38% in individuals who should not take clopidogrel

• Longstanding support for pharmacogenomic testing in the use of clopidogrel
• We implement sequencing at scale in >100k individuals across 6 health systems in the Helix Research Network (HRN)
• Using these retrospective CYP2C19 results, we stratify individuals by whether their clopidogrel treatment was appropriate in retrospect

Discovery of rare coding variants with loss of function effect using a sliding window technique on clinicogenomic data

• Power Window identifies regions in a gene or folded protein where rare variants have the same effect
• When genes show associations with LoF but not coding variants, can we identify coding variants with LoF effect?

Genetically predicted Lp(a) levels accurately identify individuals at risk of cardiovascular complications

• Lp(a) is a genetically determined cardiovascular risk factor
• It is impacted by both single nucleotide variation (SNVs) in the LPA gene as well as the number of repeats of the KIV2 exon (ranging from 1-40+)
• Previous genetic risk scores (GRS) based on SNVs have not predicted Lp(a) levels outside of European populations
• And measuring repeats of the KIV2 exon is challenging with sequencing technology In the all-comers Helix Research Network (HRN), n=108k, we develop an exome-based KIV-2 exon copy number estimate (KIV-2 CNE)
• Can a novel exome-based predictor of KIV-2 CNE accurately measure Lp(a) levels?Is genetic risk of a high Lp(a) associated directly with cardiovascular disease risk?

Genetics of Crohn’s Disease in the US population

• Inflammatory Bowel Disease (IBD), including Crohn’s disease and Ulcerative Colitis, affects ~3 million people in the US.
• Treatment often aims at reducing inflammation, with new more personalized treatments on the horizon.
• NOD2 gene is strongly associated with Crohn’s disease.
• Currently, there are no treatments or drugs that specifically target the NOD2 pathway. A few studies suggest that NOD2 homozygotes may be steroid-dependent or steroid-refractory, with potential benefits of treating with anti-TNFa.