| 1. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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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.
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| 2. |
- Lyu, Chuang, et al.
(författare)
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Expression and regulation of FRMD6 in mouse DRG neurons and spinal cord after nerve injury
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- FRMD6, a member of the group of FERM-domain proteins, is involved both in communication between cells, interactions with extracellular matrix, cellular apoptotic and regenerative mechanisms. FRMD6 was first discovered in the rodent sciatic nerve, and in the present immunohistochemical study we investigated the distribution of FRMD6 in the dorsal root ganglia (DRGs), sciatic nerve and spinal cord following sciatic nerve injury. FRMD6-immunoreactivity was found in the cytoplasm, nucleus or both, and in a majority of DRG neurons. FRMD6-immunoreactivity co-existed with several well-known neuronal markers, including calcitonin gene-related peptide, isolectin B4 and neurofilament 200 in mouse DRGs. After peripheral nerve injury, the FRMD6 mRNA levels and the overall percentage of FRMD6-positive neuron profiles (NPs) were decreased in ipsilateral lumbar DRGs, the latter mainly affecting small size neurons with cytoplasmic localization. Conversely, the proportion of NPs with nuclear FRMD6-immunoreactivity was significantly increased. In the sciatic nerve, FRMD6-immunoreactivity was observed in non-neuronal cells and in axons, and accumulated proximally to a ligation of the nerve. In the spinal cord FRMD6-immunoreactivity was detected in neurons in both dorsal and ventral horns, and was upregulated in ipsilateral dorsal horn after peripheral nerve axotomy. Our results demonstrate that FRMD6 is strictly regulated by peripheral nerve injury at the spinal level.
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| 3. |
- Svensson, Thomas, et al.
(författare)
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Association of Sleep Duration with All- And Major-Cause Mortality among Adults in Japan, China, Singapore, and Korea
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations. Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index. Design, Setting, and Participants: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. The final population included participants from Japan, China, Singapore, and Korea. Mean (SD) follow-up time was 14.0 (5.0) years for men and 13.4 (5.3) years for women. Data analysis was performed from August 1, 2018, to May 31, 2021. Exposures: Self-reported sleep duration, with 7 hours as the reference category. Main Outcomes and Measures: Mortality, including deaths from all causes, cardiovascular disease, cancer, and other causes. Sex-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression with shared frailty models adjusted for age and the key self-reported covariates of marital status, body mass index, smoking status, alcohol consumption, physical activity, history of diabetes and hypertension, and menopausal status (for women). Results: For 322721 participants (mean [SD] age, 54.5 [9.2] years; 178542 [55.3%] female), 19419 deaths occurred among men (mean [SD] age of men, 53.6 [9.0] years) and 13768 deaths among women (mean [SD] age of women, 55.3 [9.2] years). A sleep duration of 7 hours was the nadir for associations with all-cause, cardiovascular disease, and other-cause mortality in both men and women, whereas 8 hours was the mode sleep duration among men and the second most common sleep duration among women. The association between sleep duration and all-cause mortality was J-shaped for both men and women. The greatest association for all-cause mortality was with sleep durations of 10 hours or longer for both men (hazard ratio [HR], 1.34; 95% CI, 1.26-1.44) and women (HR, 1.48; 95% CI, 1.36-1.61). Sex was a significant modifier of the association between sleep duration and mortality from cardiovascular disease (χ25= 13.47, P =.02), cancer (χ25= 16.04, P =.007), and other causes (χ25= 12.79, P =.03). Age was a significant modifier of the associations among men only (all-cause mortality: χ25= 41.49, P <.001; cancer: χ25= 27.94, P <.001; other-cause mortality: χ25= 24.51, P <.001). Conclusions and Relevance: The findings of this cohort study suggest that sleep duration is a behavioral risk factor for mortality in both men and women. Age was a modifier of the association between sleep duration in men but not in women. Sleep duration recommendations in these populations may need to be considered in the context of sex and age.
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| 4. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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