Non-Coding Structural Variants in Regulatory Regions and High Polygenic Burden May Jointly Contribute to Early-Onset Familial Hashimoto’s Thyroiditis

Background/Objectives: Multigenerational families with unusually early disease onset provide a unique opportunity to investigate the genetic architecture underlying the missing heritability of complex diseases. Here, we investigated the genetic basis of apparent autosomal dominant early-onset Hashimoto’s thyroiditis (HT) in a multigenerational pedigree using whole-exome sequencing (WES) in 9 individuals and PacBio HiFi long-read whole-genome sequencing (LR-WGS) in four family members spanning three generations.