Somatic loss of the Y chromosome complements polygenic risk scores for type 2 diabetes risk prediction

Key Points

• This research aims to investigate the association between somatic loss of the Y chromosome and polygenic risk scores in relation to type 2 diabetes risk.
• Assessed germline Y haplogroups and somatic loss of Y chromosome in populations.
• Analyzed risk factors across East Asian and European men.
• Identified pancreatic β-cells exhibiting somatic loss.
• Somatic loss of Y chromosome significantly increases type 2 diabetes risk in East Asian men.
• Association is particularly strong when polygenic risk scores are low.
• Identification of LOY in pancreatic β-cells supports its role in type 2 diabetes pathogenesis.