Najaf Amin
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View article: Proteomic profiling of Alzheimer’s disease and Vascular dementia reveals unique underlying signatures
Proteomic profiling of Alzheimer’s disease and Vascular dementia reveals unique underlying signatures Open
INTRODUCTION Alzheimer’s disease (AD) and vascular dementia (VaD) account for most dementia cases. AD biomarkers remain costly and invasive, and no specific biomarkers exist for VaD. METHODS We analyzed plasma and brain proteomics in the U…
View article: Ticking Differently: Elucidating Sexual Dimorphism in Human Aging through Metabolomics, Proteomics and Genomics
Ticking Differently: Elucidating Sexual Dimorphism in Human Aging through Metabolomics, Proteomics and Genomics Open
That males and females age differently has been overlooked while developing aging clocks. Here, we developed a sex-specific metabolic aging clock in 390,941 individuals from the UK Biobank and integrated it with genetic, proteomic and epid…
View article: Association of neuroticism with incident dementia and cognitive function: 26-year follow-up of EPIC-Norfolk study
Association of neuroticism with incident dementia and cognitive function: 26-year follow-up of EPIC-Norfolk study Open
Background Neuroticism is a stable personality trait associated with increased vulnerability to mental and physical disorders. This study examined whether neuroticism is associated with the risk of dementia, particularly across the adult l…
View article: Najaf Amin: Rare coding genetic variation and downstream omics hold the key to understanding the pathogenesis of depression
Najaf Amin: Rare coding genetic variation and downstream omics hold the key to understanding the pathogenesis of depression Open
Dr. Najaf Amin stands at the forefront of depression genetics research, revolutionizing our understanding of major depression through groundbreaking multi-omics approaches that bridge molecular epidemiology and neuropsychiatry. In this exc…
View article: ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin
ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin Open
ARID1A, a subunit of the BAF chromatin remodeler, is frequently mutated in cancer. Predicting how ARID1A loss impacts cancer therapy response is challenging because it influences many cellular pathways. G quadruplex (G4) binding ligands, s…
View article: Neuroticism, omega-3 fatty acids, and risk of incident dementia
Neuroticism, omega-3 fatty acids, and risk of incident dementia Open
Neuroticism is associated with lower levels of omega-3 fatty acids, particularly DHA, which may increase dementia risk, primarily through cerebrovascular mechanisms.
View article: ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin
ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin Open
SUMMARY ARID1A is a subunit of the BAF chromatin remodelling complex that is frequently mutated in cancer. It is challenging to predict how ARID1A loss impacts cancer therapy response because it participates in many different cellular path…
View article: <i>APOE</i> stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers’s disease
<i>APOE</i> stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers’s disease Open
Among the more than 90 identified genetic risk loci for late-onset Alzheimer’s disease (AD) and related dementias, the apolipoprotein E gene ( APOE ) ɛ2/ɛ3/ɛ4 polymorphisms remains the longstanding benchmark for genetic disease risk with a…
View article: A rare variant in <i>GPR156</i> associated with depression in a Mennonite pedigree causes habenula hyperactivity and stress sensitivity in mice
A rare variant in <i>GPR156</i> associated with depression in a Mennonite pedigree causes habenula hyperactivity and stress sensitivity in mice Open
Major depressive disorder (MDD) is a leading cause of disability worldwide. Risk for MDD is heritable, and the genetic structure of founder populations enables investigation of rare susceptibility alleles with large effect. In an extended …
View article: PBRM1 directs PBAF to pericentromeres and protects centromere integrity
PBRM1 directs PBAF to pericentromeres and protects centromere integrity Open
The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventi…
View article: Varicella zoster and the risk of dementia: understanding the interplay between age, the genome and proteome
Varicella zoster and the risk of dementia: understanding the interplay between age, the genome and proteome Open
Background The mechanism through which common viruses such as varicella zoster virus (VZV) may trigger the onset of AD in the elderly is far from understood. The poliovirus receptor (PVR) is a protein of interest as it was associated to AD…
View article: Neuroticism and risk of all‐cause dementia, Alzheimer’s disease, and vascular dementia: exploring modification by genetic risk and mediation by vascular and mental health
Neuroticism and risk of all‐cause dementia, Alzheimer’s disease, and vascular dementia: exploring modification by genetic risk and mediation by vascular and mental health Open
Background Neuroticism is a personality trait that is typically stable across the life course. Higher neuroticism has been linked to a higher risk of developing dementia in studies primarily consisting of small sample sizes. There is a nee…
View article: Genome-wide association neural networks identify genes linked to family history of Alzheimer’s disease
Genome-wide association neural networks identify genes linked to family history of Alzheimer’s disease Open
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 a…
View article: Extremely rare CNVs contributing to Alzheimer disease risk: a case-control association analysis of exome sequencing data from 22,319 individuals
Extremely rare CNVs contributing to Alzheimer disease risk: a case-control association analysis of exome sequencing data from 22,319 individuals Open
Rare coding single nucleotide variants (SNV) and short insertions or deletions (indels) contribute to Alzheimer disease (AD) genetic risk, from pathogenic variants in autosomal dominant genes to risk factors with diverse effects. In contra…
View article: Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment
Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment Open
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 isoprostane…
View article: Association of neuroticism with incident dementia, neuroimaging outcomes, and cognitive function
Association of neuroticism with incident dementia, neuroimaging outcomes, and cognitive function Open
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 funct…
View article: X-Chromosome-wide association study for Alzheimer’s disease
X-Chromosome-wide association study for Alzheimer’s disease Open
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To finally address this and better characterize the genetic landscape of AD, we performed an in…
View article: DNA methylation signatures of depressive symptoms in middle-aged and elderly persons: Meta-analysis of multiethnic epigenome-wide studies
DNA methylation signatures of depressive symptoms in middle-aged and elderly persons: Meta-analysis of multiethnic epigenome-wide studies Open
Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenom…
View article: An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis
An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis Open
Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pa…
View article: Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure
Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure Open
Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP.
View article: Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants
Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants Open
Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hun…
View article: A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure Open
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our…
View article: Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose Open
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction stu…
View article: Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids Open
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wi…