Genome sequencing identifies monogenic causes in adults with metabolic diseases.

Clinical WGS in 560 adults; monogenic contribution to common metabolic diseases, with secondary findings reporting

A subset of metabolic diseases is caused by rare monogenic variants, yet diagnostic sequencing remains limited and its yield poorly known. The authors perform clinical WGS in 560 New York adults with dyslipidaemia/hypertriglyceridaemia, pre-diabetes, type 2 diabetes and/or MAFLD/MASH. Variants across a curated set of 90 monogenic genes are classified by ACMG/ClinGen, with secondary findings (v3.1) reported on consent. The cohort is diverse (18.6% African American, 22.6% Latino) and many participants have multiple conditions.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Explores under-charted ground: the monogenic contribution to common adult metabolic diseases usually considered polygenic. It fits the exome/genome direction — beyond targeted panels, capturing actionable monogenic causes in common presentations, with the associated question of secondary findings.

Analysis by Dr Thibaut Benquey