Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01

AUTHORS

Thomas J Hoffmann, Georg B Ehret, Priyanka Nandakumar, Dilrini Ranatunga, Catherine Schaefer, Pui-Yan Kwok, Carlos Iribarren, Aravinda Chakravarti, Neil Risch

ABSTRACT

Longitudinal electronic health records on 99,785 Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort individuals provided 1,342,814 systolic and diastolic blood pressure measurements for a genome-wide association study on long-term average systolic, diastolic, and pulse pressure. We identified 39 new loci among 75 genome-wide significant loci (P ≤ 5 × 10-8), with most replicating in the combined International Consortium for Blood Pressure (ICBP; n = 69,396) and UK Biobank (UKB; n = 152,081) studies. Combining GERA with ICBP yielded 36 additional new loci, with most replicating in UKB. Combining all three studies (n = 321,262) yielded 241 additional genome-wide significant loci, although no replication sample was available for these. All associated loci explained 2.9%, 2.5%, and 3.1% of variation in systolic, diastolic, and pulse pressure, respectively, in GERA non-Hispanic whites. Using multiple blood pressure measurements in GERA doubled the variance explained. A normalized risk score was associated with time to onset of hypertension (hazards ratio = 1.18, P = 8.2 × 10-45). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery. More... »

PAGES

54-64

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3715

DOI

http://dx.doi.org/10.1038/ng.3715

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003789139

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27841878


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