A polygenic risk score derived from common variants of monogenic diabetes genes is associated with young-onset type 2 diabetes and cardiovascular–kidney complications
Performance · YOD (validation cohort)Result — go to the resultOdds ratio 1.42 95% CI 1.03–1.95Authors' conclusion
Common variants of MDG increased risk for YOD and cardiovascular-kidney events.
Study context
- Population
- Discovery: 453 adults with YOD (diagnosed before age 40) and 405 without; validation: 920 YOD and 4910 non-YOD; prospective cohort of 2313 individuals with T2D
- Comparison
- Top-10% vs bottom-10% weighted polygenic risk score (wPRS) of common variants of monogenic diabetes genes
- Outcome
- Young-onset T2D (YOD); cardiovascular and kidney events
Methodological detailscase-control discovery with cross-sectional and prospective cohort validation, whole-exome sequencing, weighted polygenic risk score, independent validation cohorts
- Case-control discovery with cross-sectional and prospective cohort validation
- Whole-exome sequencing
- Weighted polygenic risk score
- Independent validation cohorts
Performance
YOD (validation cohort)
Odds ratio
1.42
95% CI 1.03–1.95
P = 0.033
Top-10%-wPRSvs Bottom-10%-wPRS
OR 1.42 (95% CI 1.03–1.95); P = 0.033
As reported in the abstract
- OR of the 135 common variants for YOD (discovery cohort) ranged
- 1.00 to 2.61
Further findings
| Outcome | Estimate | P value | |
|---|---|---|---|
| Cardiovascular-kidney events by wPRS and baseline disease duration (ref: bottom-20%-wPRS plus duration <5 years)Top-20%-wPRS plus duration 5 to <10 yearsvs Bottom-20%-wPRS plus duration <5 years | unadjusted HR 1.60 (95% CI 1.17–2.19) | P = 0.003 | |
| Cardiovascular-kidney events by wPRS and baseline disease duration (ref: bottom-20%-wPRS plus duration <5 years)Top-20%-wPRS plus duration 5 to <10 yearsvs Bottom-20%-wPRS plus duration <5 years | adjusted HR 1.62 (95% CI 1.16–2.26) | P = 0.005 | |
| Cardiovascular-kidney events by wPRS and baseline disease duration (ref: bottom-20%-wPRS plus duration <5 years)Bottom-20%-wPRS plus duration ≥10 yearsvs Bottom-20%-wPRS plus duration <5 years | unadjusted HR 1.38 (95% CI 0.97–1.98) | P = 0.075 | |
| Cardiovascular-kidney events by wPRS and baseline disease duration (ref: bottom-20%-wPRS plus duration <5 years)Bottom-20%-wPRS plus duration ≥10 yearsvs Bottom-20%-wPRS plus duration <5 years | adjusted HR 1.06 (95% CI 0.72–1.57) | P = 0.752 | |
| 0.512Ratio (log scale) |
Incident cardiovascular, kidney and cardiovascular-kidney events per standardised wPRS (2313 individuals with T2D) · median (IQR) 17.5 (14.4-21.8) years
- HR cardiovascular events
- 1.16 [95% CI 1.06, 1.27], p=0.001
- HR kidney events
- 1.09 [95% CI 1.02, 1.16], p=0.013
- HR cardiovascular-kidney events
- 1.10 [95% CI 1.03, 1.16], p=0.003
Original publication
A polygenic risk score derived from common variants of monogenic diabetes genes is associated with young-onset type 2 diabetes and cardiovascular–kidney complications. Diabetologia. Published 23 November 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →