| 1. |
- Kato, Norihiro, et al.
(författare)
-
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
-
Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
|
|
| 2. |
- Lawson, Claire A, et al.
(författare)
-
Patient-Reported Status and Heart Failure Outcomes in Asia by Sex, Ethnicity, and Socioeconomic Status
- 2023
-
Ingår i: JACC. Asia. - : Elsevier. - 2772-3747. ; 3:3, s. 349-362
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In heart failure (HF), symptoms and health-related quality of life (HRQoL) are known to vary among different HF subgroups, but evidence on the association between changing HRQoL and outcomes has not been evaluated.Objectives: The authors sought to investigate the relationship between changing symptoms, signs, and HRQoL and outcomes by sex, ethnicity, and socioeconomic status (SES).Methods: Using the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, we investigated associations between the 6-month change in a "global" symptoms and signs score (GSSS), Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS), and visual analogue scale (VAS) and 1-year mortality or HF hospitalization.Results: In 6,549 patients (mean age: 62 ± 13 years], 29% female, 27% HF with preserved ejection fraction), women and those in low SES groups had higher symptom burden but lower signs and similar KCCQ-OS to their respective counterparts. Malay patients had the highest GSSS (3.9) and lowest KCCQ-OS (58.5), and Thai/Filipino/others (2.6) and Chinese patients (2.7) had the lowest GSSS scores and the highest KCCQ-OS (73.1 and 74.6, respectively). Compared to no change, worsening of GSSS (>1-point increase), KCCQ-OS (≥10-point decrease) and VAS (>1-point decrease) were associated with higher risk of HF admission/death (adjusted HR: 2.95 [95% CI: 2.14-4.06], 1.93 [95% CI: 1.26-2.94], and 2.30 [95% CI: 1.51-3.52], respectively). Conversely, the same degrees of improvement in GSSS, KCCQ-OS, and VAS were associated with reduced rates (HR: 0.35 [95% CI: 0.25-0.49], 0.25 [95% CI: 0.16-0.40], and 0.64 [95% CI: 0.40-1.00], respectively). Results were consistent across all sex, ethnicity, and SES groups (interaction P > 0.05).Conclusions: Serial measures of patient-reported symptoms and HRQoL are significant and consistent predictors of outcomes among different groups with HF and provide the potential for a patient-centered and pragmatic approach to risk stratification.
|
|
