Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes - PubMed
9 hours ago
- #Y chromosome
- #Type 2 diabetes
- #Genetic regulation
- Study profiles germline Y haplogroups and somatic loss of the Y chromosome (LOY) in 122,683 East Asian and 181,472 European males.
- Japanese-specific haplogroup D has pleiotropic effects on height and type 2 diabetes (T2D).
- LOY increases T2D risk in East Asians but reduces it in Europeans.
- In East Asians, LOY contributes to T2D incidence, especially in males with lower polygenic risk scores.
- Incorporating sex-chromosome variation improves polygenic prediction of T2D risk in both sexes.
- Single-cell analyses show cell type-specific accumulation of LOY, with potential impairment of glucose metabolism in pancreatic β cells.
- The study highlights the clinical relevance of Y chromosome variation for diabetes risk prediction and management.