Search results for " Frequency"

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…

Haplotype reference consortium panel: Practical implications of imputations with large reference panels.

2017

Contains fulltext : 177754.pdf (Publisher’s version ) (Open Access) Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts usin…

Excessive daytime sleepiness is associated with an increased frequency of falls and sarcopenia.

2021

Background:\ud \ud This cross-sectional study aimed to examine associations between excessive daytime sleepiness (EDS) with falls and falls related conditions in older adults.\ud \ud Methods:\ud \ud To assess EDS, the Epworth Sleepiness Scale was used, with a score of ≥11/24 points indicating EDS. Number of falls and fall history (at least one) in the last year were recorded. Timed Up and Go test (TUG) was used to assess fall risk. Sarcopenia was defined by SARC-F tool. A grip strength score of the dominant hand, measured with a hand-grip dynamometer, less than 16 kg in females and 27 kg in males was accepted as dynapenia. Frailty status was defined by five dimensions including shrinking, e…

2014

Published version of an article from the journal: Food & Nutrition Research. Also available from the publisher: http://dx.doi.org/10.3402/fnr.v58.23956

The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans

2020

Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the …

In Silico Typing of Classical and Non-classical HLA Alleles from Standard RNA-Seq Reads

2018

Next-Generation Sequencing (NGS) enables the rapid generation of billions of short nucleic acid sequence fragments (i.e., "sequencing reads"). Especially, the adoption of gene expression profiling using whole transcriptome sequencing (i.e., "RNA-Seq") has been rapid. Here, we describe an in silico method, seq2HLA, that takes standard RNA-Seq reads as input and determines a sample's (classical and non-classical) HLA class I and class II types as well as HLA expression. We demonstrate the application of seq2HLA using publicly available RNA-Seq data from the Burkitt's lymphoma cell line DAUDI and the choriocarcinoma cell line JEG-3.

Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure

2021

Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10–25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case–control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants &lt

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

2017

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B.

2017

Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patien…

The rs11187533 C&amp;#x3e;T Variant of the &lt;b&gt;&lt;i&gt;FFAR4&lt;/i&gt;&lt;/b&gt; Gene Is Associated with Lower Levels of Fasting Glucose and De…

2020

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the &lt;i&gt;free fatty acid receptor 4 (FFAR4)&lt;/i&gt; gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To test the relationships of metabolic factors in children with obesity with variants of the &lt;i&gt;FFAR4&lt;/i&gt; gene. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We performed an association study of 3 single nucleotide polymorphisms (SNPs) of &lt;i&gt;FFAR4&lt;/i&gt; (rs10882273 T&amp;#x3e;C, rs1…