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- Meng, L, et al.
(författare)
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Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:12, s. 939-951
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.
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- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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- Wang, X, et al.
(författare)
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Kongcun Town Asymptomatic Intracranial Artery Stenosis study in Shandong, China: cohort profile
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:7, s. e036454-
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Tidskriftsartikel (refereegranskat)abstract
- The population-based Kongcun Town Asymptomatic Intracranial Artery Stenosis (KT-aICAS) study aims to investigate the prevalence of aICAS and major cardiovascular risk factors (CRFs) or biomarkers related to the development and prognosis of aICAS.ParticipantsThe KT-aICAS study included 2311 rural residents who were aged ≥40 years and living in Kongcun Town, Shandong Province, China. Baseline examination was conducted from October 2017 to October 2018, during which information on demographics, socioeconomics, personal and family medical history, and lifestyle factors was collected through face-to-face interviews, physical examination and blood tests. aICAS was initially screened using transcranial Doppler examination and then diagnosed using magnetic resonance angiography. Atherosclerosis in carotid arteries was diagnosed via carotid ultrasonography. High-resolution MRI was further used to evaluate the vessel wall of aICAS. Neuropsychological assessments were performed in the participants diagnosed with aICAS and the age-matched and sex-matched controls.Findings to dateOf the 2311 participants, 2027 (87.7%) completed the diagnostic procedure and aICAS was detected in 154 persons, resulting in an overall prevalence of 7.6%. The prevalence of aICAS increased with advancing age from 5.1% in participants aged 40–49 years to 12.7% in those aged ≥70 years (p<0.001). aICAS was detected in 305 intracranial arteries, including 221 (72.5%) in the anterior circulation and 84 (27.5%) in the posterior circulation (p<0.001). In addition, major CRFs were highly prevalent among middle-aged and elderly rural dwellers who were free of clinical stroke.Future plansFollow-up examinations will be performed every 3 years following the baseline examination. This study will increase our knowledge about the natural history of aICAS and facilitate studies of aICAS-associated disorders among rural-dwelling Chinese adults, such as ischaemic stroke and vascular cognitive impairment.Trial registration numberChiCTR1800017197.
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