The SG100K_Med Alliance – Clinical genetics researchers united for the analysis of Mendelian disease variation in SG100K

The project seeks a deeper understanding of genetic disease burden in major Asian populations through a larger, balanced cohort and uniform 30X Whole Genome Sequencing (WGS).

Going beyond SNVs/indels, it includes a comprehensive analysis of structural variation and short tandem repeat (STR) expansions. Leveraging research phenotypes and electronic health records, the group will demonstrate how SG100K data can resolve variants of uncertain significance (VUS).

The study will also explore the impact of polygenic backgrounds on penetrance in autosomal dominant conditions for under-represented Asian populations, where the applicability of findings from European ancestry populations is unclear.

The project aims to characterize the influence of polygenic backgrounds on conditions like hereditary breast and ovarian cancer, hypertrophic cardiomyopathy, and familial hypercholesterolemia. Additionally, the research addresses the return of results for a subset of SG100K participants, recontacting those with reportable variants (CDC Tier 1 and certain inherited cardiac conditions).

Outcomes will be presented in terms of response rates and the impact on risk management, providing practical insights into returning results within genetic research.