Search results for "nucleotide polymorphism"

2020

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, the LPA gene. Many aspects of the transcriptional regulation of LPA are poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n = 2208). We identified a CpG site in the LPA promoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n = 7512). The minor allele of rs76735376 (1.1% mi…

Genomic signatures of local adaptation to the degree of environmental predictability in rotifers

2018

AbstractEnvironmental fluctuations are ubiquitous and thus essential for the study of adaptation. Despite this, genome evolution in response to environmental fluctuations —and more specifically to the degree of environmental predictability– is still unknown. Saline lakes in the Mediterranean region are remarkably diverse in their ecological conditions, which can lead to divergent local adaptation patterns in the inhabiting aquatic organisms. The facultatively sexual rotifer Brachionus plicatilis shows diverging local adaptation in its life-history traits in relation to estimated environmental predictability in its habitats. Here, we used an integrative approach —combining environmental, phe…

Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease.

2021

BACKGROUND & AIMS: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. METHODS: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine amino transferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants wit…

The first high-density sequence characterized SNP-based linkage map of olive (Olea europaea L. subsp. europaea) developed using genotyping by sequenc…

2016

A number of linkage maps have been previously developed in olive; however, these are mostly composed of markers that have not been characterized at the sequence level, supplemented with smaller numbers of microsatellite markers. In this investigation, we sought to develop a saturated linkage mapping resource for olive composed entirely of sequence characterized markers. We employed genotyping by sequencing to develop a map of a F2 population derived from the selfing of the cultivar Koroneiki. The linkage map contained a total of 23 linkage groups comprised of 1,597 tagged SNP markers in 636 mapping bins spanning a genetic distance of 1189.7 cM. An additional 6,658 segregating SNPs were asso…

2018

Genome-Wide-Association-Studies have become a powerful method to link point mutations (e.g. single nucleotide polymorphisms (SNPs)) to a certain phenotype or a disease. However, their power to detect SNPs associated to polygenic diseases such as Alzheimer's Disease (AD) is limited, since they can only infer the pairwise relation of single SNPs to the phenotype and ignore possible effects of various SNP combinations. The common method to probe these possible complex genetic patterns is to compute a measure called linkage disequilibrium (LD). Despite the fact that several predictive patterns found with LD could successfully be applied to medical diagnosis, this measure still holds several dra…

The rs11187533 C>T Variant of the <b><i>FFAR4</i></b> Gene Is Associated with Lower Levels of Fasting Glucose and De…

2020

<b><i>Introduction:</i></b> Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the <i>free fatty acid receptor 4 (FFAR4)</i> gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease. <b><i>Objective:</i></b> To test the relationships of metabolic factors in children with obesity with variants of the <i>FFAR4</i> gene. <b><i>Methods:</i></b> We performed an association study of 3 single nucleotide polymorphisms (SNPs) of <i>FFAR4</i> (rs10882273 T>C, rs1…

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

2016

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci.METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via impu…

Shared DNA methylation signatures in childhood allergy: The MeDALL study

2021

Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…

Hereditary prostate cancer – Primetime for genetic testing?

2019

Prostate cancer (PCa) remains the most common cancer in men. The proportion of all PCa attributable to high-risk hereditary factors has been estimated to 5-15%. Recent landmark discoveries in PCa genetics led to the identification of germline mutations/alterations (eg. BRCA1, BRCA2, ATM or HOXB13), single nucleotide polymorphisms or copy number variations associated with PCa incidence and progression. However, offering germline testing to men with an assumed hereditary component is currently controversial. In the present review article, we provide an overview about the epidemiology and the genetic basis of PCa predisposition and critically discuss the significance and consequence in the cli…

Expression quantitative trait loci for PAX8 contributes to the prognosis of hepatocellular carcinoma

2017

Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment. Cox proportional hazard models …