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

Avery, Christy L.; Wassel, Christina L.; Richard, Melissa A.; Highland, Heather M.; Bien, Stephanie; Zubair, Niha; Soliman, Elsayed Z.; Fornage, Myriam; Bielinski, Suzette J.; Tao, Ran; Seyerle, Amanda A.; Shah, Sanjiv J.; Lloyd-Jones, Donald M.; Buyske, Steven; Rotter, Jerome I.; Post, Wendy S.; 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. (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), 572-80. PMCID: PMC5448160

Avery, Christy L.; Wassel, Christina L.; Richard, Melissa A.; Highland, Heather M.; Bien, Stephanie; Zubair, Niha; Soliman, Elsayed Z.; Fornage, Myriam; Bielinski, Suzette J.; Tao, Ran; Seyerle, Amanda A.; Shah, Sanjiv J.; Lloyd-Jones, Donald M.; Buyske, Steven; Rotter, Jerome I.; Post, Wendy S.; 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. (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), 572-80. PMCID: PMC5448160

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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.



JOUR



Avery, Christy L.
Wassel, Christina L.
Richard, Melissa A.
Highland, Heather M.
Bien, Stephanie
Zubair, Niha
Soliman, Elsayed Z.
Fornage, Myriam
Bielinski, Suzette J.
Tao, Ran
Seyerle, Amanda A.
Shah, Sanjiv J.
Lloyd-Jones, Donald M.
Buyske, Steven
Rotter, Jerome I.
Post, Wendy S.
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.



2017


Heart Rhythm

14

4

572-80








PMC5448160


9917

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