A custom Illumina Global Screening Array — branded Holo-Q Omniscan Waka Te Ira — was engineered with 43,437 added SNPs beyond the standard backbone, capturing 938 pathogenic familial hypercholesterolemia (FH) variants (84% of ClinVar-catalogued FH mutations), a 26.4% improvement over the standard array. The platform also incorporates 5,232 network medicine-derived coronary artery disease SNPs, 14,806 rare multi-ancestry polygenic score variants, pharmacogenomic markers across 12 drug-metabolism genes, and population-specific variants for Māori, Pacific, Asian, African, Japanese, Korean, Thai, and Russian ancestries.
This work addresses one of cardiovascular genomics' most persistent blind spots: standard polygenic risk scores trained on European cohorts perform poorly in diverse populations, systematically underestimating risk in groups already experiencing the greatest cardiovascular burden — precisely the Māori and Pacific communities bearing disproportionate CVD mortality in New Zealand. By embedding multi-ancestry content at the array design stage rather than retrofitting it statistically, the approach is architecturally sounder than post-hoc ancestry correction.
Practical limitations are real: recovery of population-specific founder variants was low, meaning rare high-impact mutations in underrepresented groups remain a detection gap — a critical caveat given FH's autosomal dominant inheritance. The array is also primarily a research and screening tool; clinical deployment requires regulatory validation pathways. As a preprint not yet peer-reviewed, the polygenic score benchmarking results — which appear truncated in the abstract — need independent scrutiny before clinical conclusions are drawn. Nonetheless, this represents a meaningful infrastructure advance for equitable precision cardiology.
