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Rare coding TTN variants are associated with electrocardiographic QT interval in the general population.

TitleRare coding TTN variants are associated with electrocardiographic QT interval in the general population.
Publication TypeJournal Article
Year of Publication2016
AuthorsKapoor A, Bakshy K, Xu L, Nandakumar P, Lee D, Boerwinkle E, Grove ML, Arking DE
Secondary AuthorsChakravarti A
JournalSci Rep
Volume6
Pagination28356
Date Published2016 06 20
ISSN2045-2322
KeywordsAfrican Americans, African Continental Ancestry Group, Alleles, Arrhythmias, Cardiac, Atherosclerosis, Chromosome Mapping, Connectin, Death, Sudden, Cardiac, Electric Conductivity, Electrocardiography, European Continental Ancestry Group, Female, Gene Deletion, Gene Frequency, Genotype, Humans, Male, Middle Aged, Myocytes, Cardiac, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Sequence Analysis, DNA, United States
Abstract

We have shown previously that noncoding variants mapping around a specific set of 170 genes encoding cardiomyocyte intercalated disc (ID) proteins are more enriched for associations with QT interval than observed for genome-wide comparisons. At a false discovery rate (FDR) of 5%, we had identified 28 such ID protein-encoding genes. Here, we assessed whether coding variants at these 28 genes affect QT interval in the general population as well. We used exome sequencing in 4,469 European American (EA) and 1,880 African American (AA) ancestry individuals from the population-based ARIC (Atherosclerosis Risk In Communities) Study cohort to focus on rare (allele frequency

DOI10.1038/srep28356
Alternate JournalSci Rep
PubMed ID27321809
PubMed Central IDPMC4913250
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
R01 GM104469 / GM / NIGMS NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL128782 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States