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- 2019
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Tidskriftsartikel (refereegranskat)
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- Butler, Anne M., et al.
(författare)
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Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
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Tidskriftsartikel (refereegranskat)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
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- He, Jia, et al.
(författare)
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A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease : the Systematic Investigation of Gastrointestinal Diseases in China
- 2010
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Ingår i: BMC Gastroenterology. - 1471-230X .- 1471-230X. ; 10, s. 94-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD. Methods: A representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/ or regurgitation occur on >= 2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on >= 1 day a week. Results: In total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (p < 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases. Conclusions: This population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries.
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- Liu, Xiaomei, et al.
(författare)
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Cognitive Benefit of a Multidomain Intervention for Older Adults at Risk of Cognitive Decline : A Cluster- Randomized Controlled Trial
- 2023
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481 .- 1545-7214. ; 31:3, s. 197-209
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We sought to assess cognitive benefits of a community-based multi -domain intervention for improving cognition among older adults at risk of cog-nitive decline (COMBAT). Design: A two-armed cluster-randomized controlled trial. Setting and Participants: Community-dwelling older adults aged 60 years or older and were at risk of cognitive decline (n = 209). Intervention: In this 9-month intervention study, 10 community hospitals in Beijing, China, were randomized (1:1) to receive either a multidomain inter-vention of meditation, cognitive training, exercise, and nutrition counseling or usual care. The intervention was delivered with weekly 1-hour group training sessions and weekly home homework. Measurements: Primary outcome was change in cognition as measured by a composite Z score of seven cognitive tests. Secondary outcomes included subjective cognitive abilities, positive and nega-tive affective experiences, physical activity, and dietary habits. Assessments were administered at baseline, end of the intervention, and 1 year after com-pleting the intervention (1-year follow-up). Results: Immediately after the intervention, the intervention group showed significant enhancement in cogni-tive performance (p = 0.026). The between-group difference in the Z score of change of cognition was 0.20 (95% CI: 0.053, 0.35), with a Hedges' g of 0.40 (95% CI: 0.29, 0.50). However, this cognitive benefit was not significant at
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- Lubitz, Steven A, et al.
(författare)
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Genetic Risk Prediction of Atrial Fibrillation
- 2017
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Ingår i: Circulation. - 0009-7322. ; 135:14, s. 1311-1320
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND—: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS—: To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10 to <1x10 in a prior independent genetic association study. RESULTS—: Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). CONCLUSIONS—: Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.
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- Newton-Cheh, Christopher, et al.
(författare)
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Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:3, s. 348-353
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
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| 8. |
- Norby, Faye L, et al.
(författare)
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Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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| 9. |
- Shi, Fangzhong, et al.
(författare)
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Seasonal compensation implied no weakening of the land carbon sink in the Northern Hemisphere under the 2015/2016 El Niño
- 2024
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Ingår i: Science China Earth Sciences. - 1674-7313 .- 1869-1897. ; 67:1, s. 294-308
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Tidskriftsartikel (refereegranskat)abstract
- The recurrent extreme El Niño events are commonly linked to reduced vegetation growth and the land carbon sink over many but discrete regions of the Northern Hemisphere (NH). However, we reported here a pervasive and continuous vegetation greening and no weakened land carbon sink in the maturation phase of the 2015/2016 El Niño event over the NH (mainly in the extra-tropics), based on multiple evidences from remote sensing observations, global ecosystem model simulations and atmospheric CO2 inversions. We discovered a significant compensation effect of the enhanced vegetation growth in spring on subsequent summer/autumn vegetation growth that sustained vegetation greening and led to a slight increase in the land carbon sink over the spring and summer of 2015 (average increases of 23.34% and 0.63% in net ecosystem exchange from two independent datasets relative to a 5-years average before the El Niño event, respectively) and spring of 2016 (6.82%), especially in the extra-tropics of the NH, where the water supply during the pre-growing-season (November of the previous year to March of the current year) had a positive anomaly. This seasonal compensation effect was much stronger than that in 1997 and 1998 and significantly alleviated the adverse impacts of the 2015/2016 El Niño event on vegetation growth during its maturation phase. The legacy effect of water supply during the pre-growing-season on subsequent vegetation growth lasted up to approximately six months. Our findings highlight the role of seasonal compensation effects on mediating the land carbon sink in response to episodic extreme El Niño events.
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| 10. |
- van Setten, Jessica, et al.
(författare)
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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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