A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK–ZNF890P locus in the Japanese general population
| Autor: | Hiroto Kikuchi, Yoichi Sutoh, Takamasa Kobayashi, Sho Hitomi, Hideki Ohmomo, Takuya Osaki, Satoru Taguchi, Atsushi Shimizu, Makoto Sasaki, Tsuyoshi Hachiya, Kenji Sobue, Yuji Takahashi, Takahito Nasu, Yoshihiro Morino, Mamoru Satoh |
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| Rok vydání: | 2021 |
| Předmět: |
Population
Genome-wide association study Locus (genetics) 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Japan Troponin T Risk Factors Genetic variation Humans Medicine 030212 general & internal medicine Allele education Genetics education.field_of_study Framingham Risk Score business.industry Repressor Proteins Cardiovascular Diseases Cohort Cardiology and Cardiovascular Medicine business Biomarkers Genome-Wide Association Study Cohort study |
| Zdroj: | International Journal of Cardiology. 329:186-191 |
| ISSN: | 0167-5273 |
| DOI: | 10.1016/j.ijcard.2020.12.019 |
| Popis: | Background Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population. Methods This was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD. Results The GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combined P value in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10−8, which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Kruppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD. Conclusions This study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population. |
| Databáze: | OpenAIRE |
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