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<p>Type 2 diabetes and hypertension are common health conditions that often occur together, suggesting shared biological mechanisms. To explore this relationship, we analyse large-scale multiomic data to uncover genetic factors underlying type 2 diabetes and blood pressure comorbidity. We curate 1304 independent single-nucleotide variants associated with type 2 diabetes and blood pressure, grouping them into five clusters related to metabolic syndrome, inverse type 2 diabetes/blood pressure risk, impaired pancreatic beta-cell function, higher adiposity, and vascular dysfunction. Colocalization with tissue-specific gene expression highlights significant enrichment in pathways related to thyroid function and fetal development. Partitioned polygenic scores derived from these clusters improve risk prediction for type 2 diabetes/hypertension comorbidity, identifying individuals with more than twice the usual susceptibility. These results reveal a mechanistically heterogeneous genetic architecture shared between type 2 diabetes and blood pressure, enhancing comorbidity risk prediction. Partitioned polygenic risk scores offer a promising approach for early risk stratification, personalised prevention, and improved management of these interconnected conditions.</p>

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Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月9日

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  • Vincent Pascat,
  • Liudmila Zudina,
  • Lucas Maurin,
  • Anna Ulrich,
  • Jared G. Maina,
  • Ayse Demirkan,
  • Zhanna Balkhiyarova,
  • Igor Pupko,
  • Yevheniya Sharhorodska,
  • François Pattou,
  • Bart Staels,
  • Marika Kaakinen,
  • Amna Khamis,
  • Amélie Bonnefond,
  • Patricia Munroe,
  • Philippe Froguel,
  • Inga Prokopenko

摘要

Type 2 diabetes and hypertension are common health conditions that often occur together, suggesting shared biological mechanisms. To explore this relationship, we analyse large-scale multiomic data to uncover genetic factors underlying type 2 diabetes and blood pressure comorbidity. We curate 1304 independent single-nucleotide variants associated with type 2 diabetes and blood pressure, grouping them into five clusters related to metabolic syndrome, inverse type 2 diabetes/blood pressure risk, impaired pancreatic beta-cell function, higher adiposity, and vascular dysfunction. Colocalization with tissue-specific gene expression highlights significant enrichment in pathways related to thyroid function and fetal development. Partitioned polygenic scores derived from these clusters improve risk prediction for type 2 diabetes/hypertension comorbidity, identifying individuals with more than twice the usual susceptibility. These results reveal a mechanistically heterogeneous genetic architecture shared between type 2 diabetes and blood pressure, enhancing comorbidity risk prediction. Partitioned polygenic risk scores offer a promising approach for early risk stratification, personalised prevention, and improved management of these interconnected conditions.