Search results for "genetic risk"
showing 10 items of 46 documents
Niedermolekulares Heparin bei Frühgeborenen mit hereditären Risikofaktoren und venösen Thrombosen
2006
We describe the use of low molecular weight heparin to treat venous thrombosis in two very low-birth-weight pre-term infants (GA: 30 and 27 weeks) both with genetic and acquired prothrombotic risk factors. Initially both infants were treated with unfractionated heparin. Since in one infant no effect on the thrombus size was observed and in the other infant there was an increase in size, the anticoagulation therapy was switched to subcutaneously injected low molecular heparin (Enoxaparin). During enoxaparin therapy the anti-Xa-level was carefully monitored and dosages were adjusted accordingly. Partial resolution of the thrombosis was achieved in both infants during enoxaparin therapy. No cl…
Impact of Parkinson's disease risk loci on age at onset
2015
Background The aim of this study was to assess whether recently identified Parkinson's disease (PD) risk genes also influence age at onset in PD. Methods We genotyped 23 single-nucleotide polymorphisms in 1,526 Danish PD patients and performed linear regression analyses with age at onset. The combined impact of PD risk loci on age at onset was assessed by linear regression analyses using a weighted genetic risk score. Results The strongest effects were observed with rs12726330 in GBA (beta = –3.63, P = 2.0 × 10−5) and rs34311866 in TMEM175/GAK (beta = –1.19, P = 4.0 × 10−3), corresponding to a 3.6-y and 1.2-y decrease of age at onset per risk allele, respectively. The weighted genetic risk …
Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis
2013
To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci sh…
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
2015
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Mapping risk factors for depression across the lifespan: An umbrella review of evidence from meta-analyses and Mendelian randomization studies
2018
The development of depression may involve a complex interplay of environmental and genetic risk factors. PubMed and PsycInfo databases were searched from inception through August 3, 2017, to identify meta-analyses and Mendelian randomization (MR) studies of environmental risk factors associated with depression. For each eligible meta-analysis, we estimated the summary effect size and its 95% confidence interval (CI) by random-effects modeling, the 95% prediction interval, heterogeneity with I 2 , and evidence of small-study effects and excess significance bias. Seventy meta-analytic reviews met the eligibility criteria and provided 134 meta-analyses for associations from 1283 primary studie…
A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse …
2017
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential assoc…
Genetic risk profiles for Alzheimer's disease: Integration of APOE genotype and variants that up-regulate inflammation
2007
BACKGROUND: A number of studies associate Alzheimer's disease with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute phase proteins. We integrated this information to better define risk and determine the relative importance of APOE and immunological mediators. METHODS: We investigated functional gene variants for APOE, IL-10 (3 loci), ACT (2 loci), HMGCR, IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma, and IL-6 found for 260 AD patients and 190 controls enrolled in Northern Italy. A fuzzy latent classification approach, namely grade-of-membership analysis (GoM), was taken to identify extreme pure type risk sets, or profiles. …
Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments.
2013
Several pathologies affect human prostate, such as prostate cancer (PC), which is the most common non-skin malignant cancer in Western male populations. A complex interaction between genetic and environmental factors (i.e. infectious agents, dietary carcinogens) and hormonal imbalances has been reported to have a fundamental role in PC pathophysiology by evoking chronic inflammation. Thus, chronic inflammation drives prostate carcinogenesis and neoplastic progression. No adequate biomarkers exist until now to guide PC prognosis and treatment. Accordingly, the research has particularly focused its attention on genetic variants in genes, codifying molecules of signaling innate immune/inflamma…
Genetic endowments, parental resources and adult health: Evidence from the Young Finns Study
2017
This paper uses longitudinal survey data linked to administrative registers to examine socioeconomic gradients in health, particularly whether the effects of genetic endowments interact with the socioeconomic resources of the parental household. We find that genetic risk scores contribute to adult health measured by biomarkers. This result is consistent with the findings from genome-wide association studies. Socioeconomic gradients in health differ based on biomarker and resource measures. Family education is negatively related to obesity and the waist-hip ratio, and family income is negatively related to low-density lipoprotein cholesterol and triglyceride levels. Parental resources do not…
IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever
2022
Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster v…