1) Common genetic variants have recently been identified through the aggregation of GWAS in large sample size, but in total these variants explain a small fraction of the heritable contribution to BP variation. For further investigation of variants associated with BP variation SardiNIA study has joined new IGCBP consortium using meta-analysis of CardioMetaboChip and IGCBP GWAS. To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 1 40,886 individuals were used for validation. We identified 66 blood pressureassociated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressurerelated pathways and highlight tissues beyond the classical renal system in blood pressure regulation. 2) We report the identification of 52 genomic loci, of which 32 are novel, reliably associated with one or more QRS phenotypes at P<110-8. These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding suggesting that they represent regions of the genome that are actively transcribed in the human heart.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000799-10
Application #
9771193
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184
van der Harst, Pim; van Setten, Jessica; Verweij, Niek et al. (2016) 52 Genetic Loci Influencing Myocardial Mass. J Am Coll Cardiol 68:1435-1448
Scuteri, Angelo; Morrell, Christopher H; Orru', Marco et al. (2016) Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study. Int J Cardiol 217:92-8
Beygui, Farzin; Wild, Philipp S; Zeller, Tanja et al. (2014) Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study. Circ Cardiovasc Genet 7:634-41
Arking, Dan E (see original citation for additional authors) (2014) Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. Nat Genet 46:826-36
Terracciano, Antonio; Strait, James; Scuteri, Angelo et al. (2014) Personality traits and circadian blood pressure patterns: a 7-year prospective study. Psychosom Med 76:237-43
Sabater-Lleal, Maria; Huang, Jie; Chasman, Daniel et al. (2013) Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease. Circulation 128:1310-24
den Hoed, Marcel (see original citation for additional authors) (2013) Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet 45:621-31
Scuteri, Angelo; Lakatta, Edward G (2013) Bringing prevention in geriatrics: evidences from cardiovascular medicine supporting the new challenge. Exp Gerontol 48:64-8
Naitza, Silvia; Porcu, Eleonora; Steri, Maristella et al. (2012) A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation. PLoS Genet 8:e1002480

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