Fine-Mapping of QT Interval Regions in Global Populations Refines Previously Identified QT Loci and Identifies Signals Unique to African and Hispanic Descent Populations

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Avery, Christy L.; Wassel, Christina L.; Richard, Melissa A.; Highland, Heather M.; Bien, Stephanie A.; Zubair, Niha; Soliman, Elsayed Z.; Fornage, Myriam; Bielinski, Suzette J.; & Tao, Ran, et al. (2017). Fine-Mapping of QT Interval Regions in Global Populations Refines Previously Identified QT Loci and Identifies Signals Unique to African and Hispanic Descent Populations. Heart Rhythm, 14(4), 572-580. PMCID: PMC5448160

Abstract

BACKGROUND: The electrocardiographically measured QT interval (QT) is heritable and its prolongation is an established risk factor for several cardiovascular DISEASES: Yet, most QT genetic studies have been performed in European ancestral populations, possibly reducing their global relevance.
OBJECTIVE: To leverage diversity and improve biologic insight, we fine-mapped 16 of the 35 previously identified QT loci (46%) in populations of African American (n=12,410) and Hispanic/Latino (n=14,837) ancestry.
METHODS AND RESULTS: The 16 fine-mapped QT loci included on the Illumina Metabochip represented 21 independent signals, of which 16 (76%) were significantly (P-value100 kb). Finally, bioinformatics-based functional characterization suggested a regulatory function in cardiac tissues for the majority of independent signals that generalized and the novel SNPs.
CONCLUSION: Our findings suggest that a majority of identified SNPs implicate gene regulatory dysfunction in QT prolongation, that the same loci influence variation in QT across global populations, and that additional, novel, population-specific QT signals exist.

URL

http://dx.doi.org/10.1016/j.hrthm.2016.12.021

Reference Type

Journal Article

Year Published

2017

Journal Title

Heart Rhythm

Author(s)

Avery, Christy L.
Wassel, Christina L.
Richard, Melissa A.
Highland, Heather M.
Bien, Stephanie A.
Zubair, Niha
Soliman, Elsayed Z.
Fornage, Myriam
Bielinski, Suzette J.
Tao, Ran
Seyerle, Amanda A.
Shah, Sanjiv J.
Lloyd-Jones, Donald M.
Buyske, Steven G.
Rotter, Jerome I.
Post, Wendy
Rich, Stephen S.
Hindorff, Lucia A.
Jeff, Janina M.
Shohet, Ralph V.
Sotoodehnia, Nona
Lin, Dan-Yu
Whitsel, Eric A.
Peters, Ulrike
Haiman, Christopher A.
Crawford, Dana C.
Kooperberg, Charles L.
North, Kari E.

PMCID

PMC5448160

ORCiD

Avery - 0000-0002-1044-8162
Highland - 000-0002-3583-8239