Pål Marius Bjørnstad

Submitted: 11 February 2026 You are already at the latest version Background: The contribution of intronic variants to the etiology of Mendelian diseases is still underrecognized, impacting the diagnostic yield. Whole genome sequencing (WGS) detects intronic variants, but beside canonical splice-sites, intronic variants are frequently excluded from the interpretation step or are classified as variants of uncertain significance (VUS).

1 Introduction Intronic variants, increasingly recognized as contributors to Mendelian diseases, are well identified by Whole-genome sequencing (WGS), but without functional validation for example using RNA-sequencing (RNA-seq), these often remain variants of uncertain significance (VUS).

Abstract Bipolar disorder is a severe neuro-psychiatric condition where genome-wide association and sequencing studies have pointed to dysregulated gene expression as likely to be causal. We observed strong correlation in expression between GWAS-associated genes and hypothesised that healthy function depends on balance in the relative expression levels of the associated genes and that patients display stoichiometric imbalance.