Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes
Authors' conclusion
Our study demonstrates the clinical relevance of Y chromosome variation for diabetes risk prediction and management.
Study context
- Population
- East Asian males from BioBank Japan and European males from the UK Biobank
- Participants
- 122,683 vs 181,472
- Comparison
- Germline Y haplogroups and somatic loss of the Y chromosome vs none
- East Asian malesn = 122,683
- European malesn = 181,472
- Outcome
- Y chromosome variation and complex traits/T2D
Methodological detailsphenome-wide scan, single-cell analyses
- Phenome-wide scan
- Single-cell analyses
Main finding
As reported in the abstract
- Male-specific genetic regulation of complex traits, incl. pleiotropic effects of Japanese-specific haplogroup D on height and T2D
- LOY increases T2D risk in East Asians but is associated with reduced T2D risk in Europeans
- In East Asians, LOY contributes to T2D incidence particularly among males with lower polygenic risk scores
- Incorporating sex-chromosome variation improves polygenic prediction of T2D risk in both sexes
Further findings
Single-cell analyses of LOY
- Cell type-specific accumulation of LOY across tissues and disease contexts; LOY in pancreatic β cells potentially impairing glucose metabolism
Original publication
Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes. Nat Med. Published 23 February 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →