James Ware

Abstract Atrial fibrillation (AF), the most common sustained arrhythmia, has a complex genetic basis; however, the molecular mechanisms linking rare and common variants remain poorly understood. Polygenic risk score (PRS) analysis in the UK Biobank and All of Us cohorts reveals that carriers of protein-altering LMNA variants (PAVs) have a significantly higher risk of incident AF than predicted by PRS alone, supporting an additive effect of common polymorphisms and LMNA variants.

Keywords return of results actionable variant founder effect exomes Orkney Shetland Introduction Where exome or genome sequencing is clinically indicated, the opportunity arises to report additional incidental findings with the aim of diagnosis and pre-emptive clinical intervention.

Rupert Woolley, Najib Rahman, James Ware Woolley R, Rahman N, Ware J. John Matthew Wrightson BMJ 2024; 387 :q2290 doi:10.1136/bmj.q2290