Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease.

Background: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2.

Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity.

Common genetic variants and susceptibility loci associated with Alzheimer's disease (AD) have been discovered through large-scale genome-wide association studies (GWAS), GWAS by proxy (GWAX) and meta-analysis of GWAS and GWAX (GWAS+GWAX). However, due to the very low repeatability of AD susceptibility loci and the low heritability of AD, these AD genetic findings have been questioned. We summarize AD genetic findings from the past 10 years and provide a new interpretation of these findings in the context of statistical heterogeneity.

rs56405341 Variant Associates with Expression of C4orf33 and C4orf33 Was Downregulated in Alzheimer's Disease and Progressive Supranuclear Palsy.

The first primary age-related tauopathy (PART) genome-wide association study confirmed significant associations of Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) genetic variants with PART, and highlighted a novel genetic variant rs56405341. Here, we perform a comprehensive analysis of rs56405341. We found that rs56405341 was significantly associated with C4orf33 mRNA expression, but not JADE1 mRNA expression in multiple brain tissues.

Causal association of genetically determined circulating vitamin D metabolites and calcium with multiple sclerosis in participants of European descent.

Background: Vitamin D is an important regulator of calcium. Mendelian randomization (MR) studies exclusively focused on the circulating total 25-hydroxyvitamin D (25(OH)D) as a biomarker of vitamin D status, and have found the causal association between 25(OH)D and the risk of multiple sclerosis (MS). However, it currently remains unclear about the causal association of the 25(OH)D subtypes including 25(OH)D3 and C3-epi-25(OH)D3, as well as calcium with the risk of MS.

An updated analysis of the association between CD2-associated protein gene rs9349407 polymorphism and Alzheimer's disease in Chinese population.

Background: Since 2011, three large-scale genome-wide association studies (GWAS) have confirmed that the CD2AP rs9349407 polymorphism is significantly connected with Alzheimer's disease (AD) in individuals of European descent. Subsequently, this association has been replicated in European populations, but is unclear whether it can be replicated in Chinese. Recently, the correlation between rs9349407 and AD in the Chinese population has become a research hotspot.

White blood cell count and chronic obstructive pulmonary disease: A Mendelian Randomization study.

Blood leukocyte counts (e.g., eosinophil count) are important biomarkers for the onset, classification, and exacerbation of chronic obstructive pulmonary disease (COPD).

Evaluating the Bidirectional Causal Association Between Daytime Napping and Alzheimer's Disease Using Mendelian Randomization.

Background: Until now, both cross-sectional and longitudinal studies have identified controversial findings about the association between daytime napping and Alzheimer's disease (AD) or cognitive decline. Therefore, it remains unclear about the causal association between daytime napping and AD or cognitive decline.

Objective: We aim to investigate the causal association between daytime napping and AD.

Parkinson's Disease rs117896735 Variant Regulates INPP5F Expression in Brain Tissues and Increases Risk of Alzheimer's Disease.

Background: Both INPP5D and INPP5F are members of INPP5 family. INPP5F rs117896735 variant was associated with Parkinson's disease (PD) risk, and INPP5D was an Alzheimer's disease (AD) risk gene. However, it remains unclear about the roles of INPP5F rs117896735 variant in AD.

Cognitive performance protects against Alzheimer's disease independently of educational attainment and intelligence.

Mendelian-randomization (MR) studies using large-scale genome-wide association studies (GWAS) have identified causal association between educational attainment and Alzheimer's disease (AD). However, the underlying mechanisms are still required to be explored. Here, we conduct univariable and multivariable MR analyses using large-scale educational attainment, cognitive performance, intelligence and AD GWAS datasets.

Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX.

Background: Until now, Mendelian randomization (MR) studies have investigated the causal association of risk factors with Alzheimer's disease (AD) using large-scale AD genome-wide association studies (GWAS), GWAS by proxy (GWAX), and meta-analyses of GWAS and GWAX (GWAS+GWAX) datasets. However, it currently remains unclear about the consistency of MR estimates across these GWAS, GWAX, and GWAS+GWAX datasets.

Methods: Here, we first selected 162 independent educational attainment genetic variants as the potential instrumental variables (N = 405,072).

Single-Cell Transcriptome Profiles Reveal Fibrocytes as Potential Targets of Cell Therapies for Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is potentially life-threatening in aging population due to the risk of aortic rupture and a lack of optimal treatment. The roles of different vascular and immune cells in AAA formation and pathogenesis remain to be future characterized. Single-cell RNA sequencing was performed on an angiotensin (Ang) II-induced mouse model of AAA.

Mendelian randomization to evaluate the effect of plasma vitamin C levels on the risk of Alzheimer's disease.

Objective: Until now, observational studies have explored the impact of vitamin C intake on Alzheimer's disease (AD) risk, however, reported ambiguous findings. To develop effective therapies or prevention, the causal link between vitamin C levels and AD should be established.

Methods: Here, we selected 11 plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (N = 52,018) as the potential instrumental variables.

Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown.

Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown.

Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study.

Background: Until now, epidemiological evidence regarding the association between vitamin C intake (both diet and supplements) and Parkinson's disease (PD) remains inconsistent. Hence, it is necessary to establish the causal link between vitamin C levels and PD, and further develop effective therapies or prevention.

Methods: We selected 11 newly identified plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (n = 52,018) as the effective instrumental variables, and extracted their corresponding GWAS summary statistics from PD (33,674 PD cases and 449,056 controls) and PD age at onset (AAO) (n = 28,568).

PLCG2 rs72824905 Variant Reduces the Risk of Alzheimer's Disease and Multiple Sclerosis.

We aimed to evaluate the association of PLCG2 rs72824905 variant with Alzheimer's disease (AD) and multiple sclerosis (MS) using large-scale genetic association study datasets. We selected 50,024 AD cases and 467,330 controls, and 32,367 MS cases and 36,012 controls. We found moderate heterogeneity of rs72824905 in different studies.

rs1990622 variant associates with Alzheimer's disease and regulates TMEM106B expression in human brain tissues.

Background: It has been well established that the TMEM106B gene rs1990622 variant was a frontotemporal dementia (FTD) risk factor. Until recently, growing evidence highlights the role of TMEM106B in Alzheimer's disease (AD). However, it remains largely unclear about the role of rs1990622 variant in AD.

Stroke and Alzheimer's Disease: A Mendelian Randomization Study.

Stroke and Alzheimer's disease (AD) are common neurological diseases. Several exiting studies indicated that late onset-AD and ischemic stroke have shared genetic links. Different kinds of stroke have different mechanisms.

Mendelian randomization study to evaluate the effects of interleukin-6 signaling on four neurodegenerative diseases.

Background: Multiple sclerosis (MS) is a complex neurological disease and chronic inflammatory disease. Until now, observational studies have reported positive association between serum interleukin-6 (IL-6) levels and MS risk. In order to develop effective therapies, we should establish the causal link between IL-6 signaling and MS.