Search results for "Association."
showing 10 items of 1723 documents
Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes
2012
One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1…
Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder.
2013
Abstract Background Dysfunctions of serotonergic neurotransmission are supposed to be involved in the pathogenesis of psychiatric disorders such as major depressive disorder (MDD). The concentration of serotonin (5-hydroxytryptamine, 5-HT) in the synaptic cleft is essentially regulated by the 5-HT transporter (5-HTT). A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders. Methods Genotyping of the 5-HTTLPR is time-consuming and technically challenging. Recently, a two-SNP haplotype was identified that tags the 5-HTTLPR at r 2 =0.775. This allows extraction of 5-HTTLPR genotype information from…
Social exclusion influences conditioned fear acquisition and generalization: A mediating effect from the medial prefrontal cortex
2020
Abstract Fear acquisition and generalization play key roles in promoting the survival of mammals and contribute to anxiety disorders. While previous research has provided much evidence for the repercussions of social exclusion on mental health, how social exclusion affects fear acquisition and generalization has received scant attention. In our study, participants were divided into two groups according to two Cyberball paradigm conditions (exclusion/inclusion). Both groups underwent a Pavlovian conditioning paradigm, functional near-infrared spectroscopy (fNIRS), and skin conductance response (SCR) assessments. We aimed to determine the effects of social exclusion on fear acquisition and ge…
An Intergenic rs9275596 Polymorphism on Chr. 6p21 Is Associated with Multiple Sclerosis in Latvians
2020
Background and objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to demyelination of neurons and potentially debilitating physical and mental symptoms. The disease is more prevalent in women than in men. The major histocompatibility complex (MHC) region has been identified as a major genetic determinant for autoimmune diseases, and its role in some neurological disorders including MS was evaluated. An intergenic single-nucleotide polymorphism (SNP), rs9275596, located between the HLA-DQB1 and HLA-DQA2 genes, is in significant association with various autoimmune diseases according to genome-wide association studies (GWASs). A cumulat…
Integration of cognitive allocentric information in visuospatial short-term memory through the hippocampus
2005
Visuospatial short-term memory relies on a widely distributed neocortical network: some areas support the encoding process of the visually acquired spatial information, whereas other ares are more involved in the active maintenance of the encoded information. Recently, in a pointing to remembered targets task, it has been shown in healthy subjects that, for memory delays of 5 s, spatial errors are affected also by cognitive allocentric information, i.e., covert spatial information derived from a pure mental representation. We tested the effect of a lesion of the hippocampus on the accuracy of pointing movements toward remembered targets, with memory delays falling in the 0.5-30 s range. The…
NDST1 missense mutations in autosomal recessive intellectual disability.
2014
NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in …
Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain.
2014
Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases wit…
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
2018
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 ca…
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
2011
1. The CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genetics. 2011;43:333–338. ### Study Hypothesis Recently, genome-wide association studies (GWAS) have identified several common variants that are associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). The authors state that the current loci discovered in CAD and MI GWAS explain only a small fraction of the heritability of this complex disease. The authors hypothesized that a larger study would provide more power to discover common variants with modest effect sizes. Therefore, they formed the Coronary ARtery DIsease Genome-wid…
Neural dynamics of learning sound-action associations.
2008
A motor component is pre-requisite to any communicative act as one must inherently move to communicate. To learn to make a communicative act, the brain must be able to dynamically associate arbitrary percepts to the neural substrate underlying the pre-requisite motor activity. We aimed to investigate whether brain regions involved in complex gestures (ventral pre-motor cortex, Brodmann Area 44) were involved in mediating association between novel abstract auditory stimuli and novel gestural movements. In a functional resonance imaging (fMRI) study we asked participants to learn associations between previously unrelated novel sounds and meaningless gestures inside the scanner. We use functio…