Publications

BibTex format

@article{Tremblay:2021:10.1007/s00125-021-05491-7,
author = {Tremblay, J and Haloui, M and Attaoua, R and Tahir, R and Hishmih, C and Harvey, F and Marois-Blanchet, F-C and Long, C and Simon, P and Santucci, L and Hizel, C and Chalmers, J and Marre, M and Harrap, S and Cifkova, R and Krajcoviechova, A and Matthews, DR and Williams, B and Poulter, N and Zoungas, S and Colagiuri, S and Mancia, G and Grobbee, DE and Rodgers, A and Liu, L and Agbessi, M and Bruat, V and Fave, M-J and Harwood, MP and Awadalla, P and Woodward, M and Hussin, JG and Hamet, P},
doi = {10.1007/s00125-021-05491-7},
journal = {Diabetologia},
pages = {2012--2025},
title = {Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control},
url = {http://dx.doi.org/10.1007/s00125-021-05491-7},
volume = {64},
year = {2021}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Aims/hypothesisType 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk.MethodsWe developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study.ResultsThe model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years.Conclusions/interpretationThis novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.
AU  - Tremblay,J
AU  - Haloui,M
AU  - Attaoua,R
AU  - Tahir,R
AU  - Hishmih,C
AU  - Harvey,F
AU  - Marois-Blanchet,F-C
AU  - Long,C
AU  - Simon,P
AU  - Santucci,L
AU  - Hizel,C
AU  - Chalmers,J
AU  - Marre,M
AU  - Harrap,S
AU  - Cifkova,R
AU  - Krajcoviechova,A
AU  - Matthews,DR
AU  - Williams,B
AU  - Poulter,N
AU  - Zoungas,S
AU  - Colagiuri,S
AU  - Mancia,G
AU  - Grobbee,DE
AU  - Rodgers,A
AU  - Liu,L
AU  - Agbessi,M
AU  - Bruat,V
AU  - Fave,M-J
AU  - Harwood,MP
AU  - Awadalla,P
AU  - Woodward,M
AU  - Hussin,JG
AU  - Hamet,P
DO  - 10.1007/s00125-021-05491-7
EP  - 2025
PY  - 2021///
SN  - 0012-186X
SP  - 2012
TI  - Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-021-05491-7
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000669749700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007%2Fs00125-021-05491-7
UR  - http://hdl.handle.net/10044/1/90474
VL  - 64
ER  -

Download

Professor Neil Poulter

Contact

Assistant

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)