Meta-Prediction of the Effect of Methylenetetrahydrofolate Reductase Polymorphisms and Air Pollution on Alzheimer’s Disease Risk

Background: Alzheimer’s disease (AD) is a significant public health issue. AD has been linked with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, but the findings have been inconsistent. The purpose of this meta-predictive analysis is to examine the associations between MTHFR polymorphisms and epigenetic factors, including air pollution, with AD risk using big data analytics approaches. Methods and Results: Forty-three studies (44 groups) were identified by searching various databases. MTHFR C677T TT and CT genotypes had significant associations with AD risk in all racial populations (RR = 1.13, p = 0.0047; and RR = 1.12, p < 0.0001 respectively). Meta-predictive analysis showed significant increases of percentages of MTHFR C677T polymorphism with increased air pollution levels in both AD case group and control group (p = 0.0021–0.0457); with higher percentages of TT and CT genotypes in the AD case group than that in the control group with increased air pollution levels. Conclusions: The impact of MTHFR C677T polymorphism on susceptibility to AD was modified by level of air pollution. Future studies are needed to further examine the effects of gene-environment interactions including air pollution on AD risk for world populations

Experiences of Living in the Community for Older Aboriginal Persons With Dementia Symptoms in Taiwan

[[abstract]]Background and Objectives Improving quality of life for community-dwelling older persons with dementia symptoms (PWDS) and family caregivers requires promoting dementia-friendly communities (DFC). However, little is known regarding older Taiwanese Aboriginal PWDS’ experiences of living in the community. We explored these experiences for older Atayal PWDS and their families in Taiwan. Research Design and Methods This grounded theory research used in-depth interviews to explore the perspectives of older PWDS (n = 4), their family members (n = 3), and key persons (n = 10) in an Atayal community in northern Taiwan. Data were analyzed using constant comparative analysis. Participants were interviewed between January and May 2015. Results Participants’ experiences were captured by the overarching concept of “low dementia awareness, high family-like ambience in the community.” Despite the low/absent community awareness of dementia, older Atayal PWDS functioned as freely in the community as at home due to a family-like supportive environment. Aboriginal PWDS and their families also faced environmental challenges, e.g., environmental constraints and barriers to transportation access. Discussion and Implications Our results suggest that this Aboriginal community and culture offer important DFC components, and these strengths could be further studied to enhance DFC models elsewhere. Despite these strengths in supporting PWDS, environmental challenges to transportation access still cause difficulties for PWDS and their families and need improvement. The Atayal community’s low dementia awareness suggests that services introduced must be culturally appropriate and nondisruptive to existing supportive helping systems. Our study can be a model for future studies to understand and identify PWDS’ needs in Indigenous communities

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease