Publications by authors named "Najaf Amin"

Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging.

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Augmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce "genome-wide association neural networks (GWANN)" a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer's disease (AD). In UK Biobank, we defined cases (n = 42 110) as those with AD or family history of AD and sampled an equal number of controls.

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  • A study was conducted to investigate the X-chromosome's role in Alzheimer's Disease (AD), which had been overlooked in previous genome-wide association studies.
  • The research included 115,841 AD cases and 613,671 controls, considering different X-chromosome inactivation (XCI) states in females.
  • While no strong genetic risk factors for AD were found on the X-chromosome, seven significant loci were identified, suggesting areas for future research.
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  • Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
  • Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
  • The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
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  • Circulating plasma proteins are crucial for human health and can help measure biological age, which may predict risks for age-related diseases and overall mortality.
  • A study using data from the UK Biobank identified 204 proteins that accurately predict chronological age and are linked to 18 chronic diseases, as well as various health measures such as cognitive function and frailty.
  • The findings were validated in studies from China and Finland, showing that this proteomic age clock can reliably assess age-related health risks across different populations.
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Background: Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.

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Introduction: Higher neuroticism might be associated with dementia risk. Here we investigated modification by genetic predisposition to dementia, mediation by mental health and vascular conditions, neuroimaging outcomes, and cognitive function.

Methods: Cox proportional-hazards models were used to assess the association between neuroticism score and incident dementia over up to 15 years in 1,74,164 participants.

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Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases.

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  • Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
  • The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
  • Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
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Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression.

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Introduction: The number of people with dementia and stroke is increasing worldwide. There is increasing evidence that there are clinically relevant genetic differences across ethnicities. This study aims to quantify risk factors of dementia, stroke, and mortality in Asian and black participants compared to whites.

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Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.

Objective: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD.

Design, Setting And Participants: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics.

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  • This study looked at how body size and shape traits, like height and BMI, can be linked to genetics and health problems related to the heart and metabolism.! -
  • Scientists analyzed DNA from over 22,000 people to find genetic connections to these traits and discovered some specific genes that might affect height and BMI.! -
  • They found important results related to height but faced difficulties in identifying the effects of rare genetic variants, which are harder to study but still important for understanding genetics.!
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Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate the relation of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from the Rotterdam Study cohort and validate these findings in the Amsterdam HELIUS cohort in 1,539 subjects.

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There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients.

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Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls.

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Background: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.

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Background: Research on the association between physical inactivity and cognitive decline and dementia is dominated by studies with short-term follow-up, that might be biased by reverse causality.

Objective: Investigate the long-term association between physical activity, cognition, and the rate of age-associated cognitive decline.

Methods: We investigated the association between late-life physical activity and executive functioning and rate of decline of executive abilities during follow-up of up to 16 years, in 3553 participants of the prospective Rotterdam Study cohort.

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  • Understanding the genetic basis of memory could help address neurodegenerative disorders, and a study examined this in a large group of adults without dementia or stroke (N=53,637).
  • Researchers identified new genetic locations associated with verbal short-term memory and learning, particularly in the genes CDH18 and APOE/APOC1/TOMM40, with results verified in a separate sample.
  • Analysis showed that a genetic score for verbal learning correlated with brain activity during memory tasks and linked memory traits to various cognitive and health outcomes.
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Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

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  • There is increasing evidence that gut microbiota plays a significant role in various health issues, particularly neuropsychiatric diseases like autism, major depression, and schizophrenia.
  • A systematic review analyzed 50 studies involving over 2,000 patients and highlighted certain genera of microbiota that showed notable changes in abundance related to these conditions.
  • The findings suggest a complex connection between gut health and brain function, indicating potential for targeted probiotic or antibiotic treatments to address neuropsychiatric disorders.
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Background: Genetic variants within the APOE locus may modulate Alzheimer's disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality.

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Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging.

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  • Telomeres, which are repetitive DNA sequences at chromosome ends, are linked to aging, diseases, and mortality, with lipid and fatty acid metabolism possibly contributing to their shortening.
  • This study analyzed 226 metabolic biomarkers in a large sample of 11,775 individuals to examine their association with leukocyte telomere length (LTL), using sophisticated methods like regression analysis and meta-analysis for robust findings.
  • Four metabolic biomarkers, particularly certain cholesterol ratios in small VLDL and omega-6 fatty acid ratios, were positively associated with LTL, suggesting that lipid and fatty acid metabolism may play critical roles in telomere biology, although further longitudinal studies are required to confirm these findings and rule out reversed causation.
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