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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

ABSTRACT: Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

SUBMITTER: Warren HR 

PROVIDER: S-EPMC5972004 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

Warren Helen R HR   Evangelou Evangelos E   Cabrera Claudia P CP   Gao He H   Ren Meixia M   Mifsud Borbala B   Ntalla Ioanna I   Surendran Praveen P   Liu Chunyu C   Cook James P JP   Kraja Aldi T AT   Drenos Fotios F   Loh Marie M   Verweij Niek N   Marten Jonathan J   Karaman Ibrahim I   Lepe Marcelo P Segura MP   O'Reilly Paul F PF   Knight Joanne J   Snieder Harold H   Kato Norihiro N   He Jiang J   Tai E Shyong ES   Said M Abdullah MA   Porteous David D   Alver Maris M   Poulter Neil N   Farrall Martin M   Gansevoort Ron T RT   Padmanabhan Sandosh S   Mägi Reedik R   Stanton Alice A   Connell John J   Bakker Stephan J L SJ   Metspalu Andres A   Shields Denis C DC   Thom Simon S   Brown Morris M   Sever Peter P   Esko Tõnu T   Hayward Caroline C   van der Harst Pim P   Saleheen Danish D   Chowdhury Rajiv R   Chambers John C JC   Chasman Daniel I DI   Chakravarti Aravinda A   Newton-Cheh Christopher C   Lindgren Cecilia M CM   Levy Daniel D   Kooner Jaspal S JS   Keavney Bernard B   Tomaszewski Maciej M   Samani Nilesh J NJ   Howson Joanna M M JM   Tobin Martin D MD   Munroe Patricia B PB   Ehret Georg B GB   Wain Louise V LV  

Nature genetics 20170130 3

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet  ...[more]

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