Approved Research

Sex-specific genome-wide association study of hypertensive hyperuricemic individuals developing cardiovascular events or Alzheimer's disease

Lay summary

The increase in life expectancy and the resulting aging of the population make it imperative to implement preventive and therapeutic strategies aimed at preserving the physical and cognitive integrity of adults and the elderly. Cardiovascular diseases and Alzheimer's disease (AD) are chronic and debilitating conditions that contribute largely to the burden of morbidity and cognitive disability and that unequally affect men and women. This sexual disparity may result from several factors, including sex-driven differences in genetic variation and gene expression at the level of complex traits involved in disease development, like blood pressure and uric acid profiles. Blood pressure is a sexually dimorphic trait, and increased blood pressure is a well established cardiovascular risk factor. In parallel, uric acid was associated with neuroprotective effects and improved cognitive performance, but it is  also emerging as a contributor to cardiovascular diseases and related mortality in a sex-specific manner. UK Biobank creates a unique opportunity to test whether sex-specific genetic features exist in men versus women with hypertension and hyperuricemia who develop major cardiovascular events or AD. We plan to use the genetic and clinical information from the repository to identify novel genetic variants associated with the phenotypes of interest, examine whether variants have effects on the phenotypes in a sexually dimorphic manner, and test interactions between variants and other relevant characteristics (e.g. age, adiposity, comorbidities, smoking habits, markers of systemic inflammation). We estimate that 3 years are needed to complete the study. Our proposal may contribute to the understanding of sex-specific genetic signatures behind disease trajectories and contribute to preventive medicine and to potential novel therapeutic approaches to common and devastating conditions like cardiovascular diseases and AD.