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- Teumer, A, et al.
(author)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Journal article (peer-reviewed)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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- Waterink, L, et al.
(author)
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Changes in Brain-Health Related Modifiable Risk Factors in Older Adults After One Year of COVID-19-Restrictions
- 2022
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In: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13, s. 877460-
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has major influence on lifestyle and mental health, which might affect brain-health and increase the risk of cognitive decline, particularly in older adults. We aimed to describe changes in modifiable risk factors related to brain-health in older adults after one year of COVID-19 restrictions.MethodsAn online survey was disseminated between February and March 2021 to 17,773 registrants of the Dutch Brain Research Registry, aged ≥50, without a self-reported diagnosis of mild cognitive impairment or dementia. Participants were asked to report potential changes in behaviors during the COVID-19 pandemic, compared to pre-pandemic, in eight domains related to brain health: physical activity, sleep, feeling of memory decline, perceived stress, feeling of loneliness, diet, alcohol consumption, and smoking. We used negative binomial regression analyses to relate (socio)demographics, subjective memory complaints and COVID-19 related aspects (fear of, or current/past COVID-19 infection) to the number of reported detrimental and beneficial changes as dependent variable.Results3,943 participants (66 ± 8 years old; 76% female; 71% highly educated) completed the survey. After one year of COVID-19-restrictions, 74% reported at least one detrimental lifestyle change unfavorable for their brain health, most frequently reported were feelings of loneliness, sleep problems, and less physical activity. 60% of participants reported at least one beneficial change, which were most often more physical activity, healthier dietary habits, and less alcohol consumption. Individuals who are younger [incidence rate ratio (IRR) = 0.99, 95% CI = 0.98–0.99], female (1.20, 1.11–1.30), living alone (1.20, 1.11–1.28) and in urban environments (1.18, 1.08–1.29), who are less satisfied with their income (1.38, 1.17–1.62), experiencing subjective memory complaints (1.40, 1.28–1.52) and those with a past or current (1.19, 1.06–1.34) or fear of a COVID-19 infection (1.33, 1.25–1.42) reported higher numbers of detrimental changes.DiscussionThe COVID-19 pandemic has influenced lifestyle in both positive and negative ways. We identified (socio)demographic factors associated with more detrimental changes in modifiable risk factors related to brain health, suggesting that some individuals are more vulnerable for the impact of the COVID-19 pandemic. These findings provide an opportunity for targeted prevention and education to promote a healthy lifestyle during and after the pandemic.
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- Niemi, MEK, et al.
(author)
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- 2021
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