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Genetic information can be used to enable early detection of risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20096.3\u2009\u00d7\u200910\n                      <jats:sup>\u221221<\/jats:sup>\n                      and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20099.6\u2009\u00d7\u200910\n                      <jats:sup>\u221231<\/jats:sup>\n                      , respectively) and a 4.4-fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20096.8\u2009\u00d7\u200910\n                      <jats:sup>\u221233<\/jats:sup>\n                      ) 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\u00a0years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-021-05491-7","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T19:03:40Z","timestamp":1625511820000},"page":"2012-2025","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose 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