期刊
JOURNAL OF HYPERTENSION
卷 33, 期 4, 页码 669-680出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000000479
关键词
epistasis; genetics of hypertension; quantitative trait locus discovery; regulatory hierarchy
资金
- Canadian Institutes of Health Research
Essential hypertension is one of the most common disorders that underpin significant morbidity and mortality however, underlying mechanisms remain elusive that either dictate the actions of individual quantitative trait loci (QTLs) or engineer the overall genetic architecture from them. Recent experimental evidence has unveiled that the genetic architecture determining blood pressure (BP) is assembled from QTL-building blocks by epistasis into regulatory hierarchies. BP, a polygenic and quantitative trait is homeostasized via pathways participated by Mendelian constituents that operate distantly from end-phase physiological genes. Epistasis genetics performed in the current article has mechanistically unravelled the order and regulatory relationships between certain BP QTLs, and is the first study ever conducted in a mammalian system in analysing a complex trait. The elucidation of the sequence of event and regulatory hierarchies of QTL actions in these pathways will facilitate mechanism-based diagnoses and cause-driven treatments for essential hypertension.
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