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Identification of Functional Genetic Determinants of Cardiac Troponin T and I in a Multiethnic Population and Causal Associations With Atrial Fibrillation.

Friday,2022-03-04 22:39 America/Los_Angeles — ecterry
TitleIdentification of Functional Genetic Determinants of Cardiac Troponin T and I in a Multiethnic Population and Causal Associations With Atrial Fibrillation.
Publication TypeJournal Article
Year of Publication2021
AuthorsYang, Y, Bartz, TM, Brown, MR, Guo, X, Zilhão, NR, Trompet, S, Weiss, S, Yao, J, Brody, JA, deFilippi, CR, Hoogeveen, RC, Lin, HJ, Gudnason, V, Ballantyne, CM, Dörr, M, J Jukema, W, Petersmann, A, Psaty, BM, Rotter, JI, Boerwinkle, E, Fornage, M, Jun, G, Yu, B
JournalCirc Genom Precis Med
Volume14
Issue6
Paginatione003460
Date Published2021 12
ISSN2574-8300
Abstract<p><b>BACKGROUND: </b>Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive.</p><p><b>METHODS: </b>We conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI.</p><p><b>RESULTS: </b>We identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in and 3 previously reported loci at , , and . One known locus at was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18; =2.80×10). We observed pleiotropic loci located at and . The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with expression in heart tissues and hs-cTnT and with expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25-1.54] for hs-cTnT and 1.21 [95% CI, 1.06-1.37] for hs-cTnI).</p><p><b>CONCLUSIONS: </b>We identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation.</p>
DOI10.1161/CIRCGEN.121.003460
Alternate JournalCirc Genom Precis Med
PubMed ID34732054
PubMed Central IDPMC8692416
Grant List75N95020D00003 / DA / NIDA NIH HHS / United States
75N92022D00007 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
75N95020D00004 / DA / NIDA NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
75N90020D00002 / CL / CLC NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
75N96020D00002 / ES / NIEHS NIH HHS / United States
75N93020D00002 / AI / NIAID NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
75N99020D00003 / OF / ORFDO NIH HHS / United States
75N95020D00002 / DA / NIDA NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
R01 DK118631 / DK / NIDDK NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
75N90020D00003 / CL / CLC NIH HHS / United States
75N96020D00003 / ES / NIEHS NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
75N99020D00002 / OF / ORFDO NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
75N99020D00006 / OF / ORFDO NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
75N95020D00007 / DA / NIDA NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
R03 HD098552 / HD / NICHD NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
75N95020D00005 / DA / NIDA NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
75N99020D00005 / OF / ORFDO NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
R01 HL148218 / HL / NHLBI NIH HHS / United States
75N99020D00007 / OF / ORFDO NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
R01 HL141824 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
75N98020D00007 / OD / NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
75N99020D00004 / OF / ORFDO NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
ePub date: 
21/12

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