Search results for " Multifactorial Inheritance"

showing 4 items of 4 documents

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

2021

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic …

0301 basic medicineOncologyLiver CirrhosisMaleMultifactorial InheritanceCirrhosis0302 clinical medicineRisk FactorsNon-alcoholic Fatty Liver DiseaseHepatic fatAdiposityeducation.field_of_studyFatty liverLiver NeoplasmsMiddle AgedPrognosisEuropeCirrhosisLiverCohort030211 gastroenterology & hepatologyBiomarker; Cirrhosis; Genetics; Hepatic fat; Non-alcoholic fatty liver diseaseFemaleLiver cancerCohort studymedicine.medical_specialtyCarcinoma HepatocellularSettore MED/12 - GASTROENTEROLOGIAPopulationRisk Assessment03 medical and health sciencesBiomarker Cirrhosis Genetics Hepatic fat Non-alcoholic fatty liver disease Cross-Sectional Studies Europe Female Genetic Predisposition to Disease Humans Liver Liver Cirrhosis Male Mediation Analysis Middle Aged Multifactorial Inheritance Predictive Value of Tests Prognosis Risk Assessment Risk Factors Adiposity Carcinoma Hepatocellular Non-alcoholic Fatty Liver DiseaseGeneticPredictive Value of TestsInternal medicinemedicineGenetic predispositionGeneticsHumansGenetic Predisposition to DiseaseeducationCirrhosiMediation AnalysisHepatologybusiness.industryCarcinomaCase-control studyHepatocellularBiomarkermedicine.diseasedigestive system diseases030104 developmental biologyCross-Sectional StudiesbusinessJournal of Hepatology
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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…

AdultMaleMultifactorial InheritanceQUANTITATIVE TRAIT LOCUSGenotypeSEQUENCING DATAQuantitative Trait LociSUSCEPTIBILITYPolymorphism Single NucleotideArticleCohort StudiesCODING VARIANTSCrohn Disease80 and overJournal ArticleMedicine and Health SciencesLOCUSHumansGenetic Predisposition to DiseasePolymorphismGENOME-WIDE ASSOCIATIONGenetic Association StudiesAgedAged 80 and overScience & TechnologyAdult; Aged; Aged 80 and over; Cohort Studies; Crohn Disease; Female; Gene Expression Profiling; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Polymorphism Single Nucleotide; Quantitative Trait Loci; Sequence Analysis DNA; Multifactorial InheritanceGene Expression ProfilingCOMPLEX TRAITSBiology and Life SciencesSequence Analysis DNASingle NucleotideDNAMiddle AgedInflammatory Bowel DiseasesCROHNS-DISEASEMultidisciplinary SciencesQUANTITATIVE TRAITRARE VARIANTSScience & Technology - Other TopicsFemaleLOW-FREQUENCYSequence AnalysisINFLAMMATORY-BOWEL-DISEASE
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Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial…

2022

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) wer…

MaleAdultMultifactorial InheritanceSettore MED/09 - Medicina Internafamilial hypercholesterolemia; molecular diagnosis; polygenic risk score; Adult; Cholesterol LDL; Female; Humans; Middle Aged; Multifactorial Inheritance; Mutation; Gene Regulatory Networks; Hyperlipoproteinemia Type IIfamilial hypercholesterolemiaCholesterol LDLMiddle AgedLDLHyperlipoproteinemia Type IICholesterolmolecular diagnosispolygenic risk scoreMutationHumansFemaleGene Regulatory Networksmolecular diagnosifamilial hypercholesterolemia; molecular diagnosis; polygenic risk score
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

2019

International audience; Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional g…

OncologyMaleMultifactorial InheritanceLymphomaEpidemiologyChronic lymphocytic leukemiaFollicular lymphomaGenome-wide association studyDiseaseNeurodegenerativemeta-analysiimmune system diseasesHLA AntigensRisk Factorshemic and lymphatic diseases2.1 Biological and endogenous factorsHLA AntigenAetiologyGenetics (clinical)CancerAllele0303 health sciences[SDV.MHEP] Life Sciences [q-bio]/Human health and pathologyLymphoma Non-Hodgkinnon-Hodgkin lymphoma030305 genetics & hereditySingle NucleotideHematologyMiddle Aged3. Good healthnon-Hodgkin lymphoma.Public Health and Health ServicesFemaleHumanmedicine.medical_specialtyautoimmune disease; genome-wide association study; meta-analysis; non-Hodgkin lymphoma; Alleles; Autoimmune Diseases; Female; HLA Antigens; Humans; Lymphoma Non-Hodgkin; Male; Middle Aged; Multifactorial Inheritance; Polymorphism Single Nucleotide; Risk Factors; Genetic Predisposition to DiseaseNon-Hodgkinautoimmune diseasePolymorphism Single NucleotideArticleAutoimmune Diseases03 medical and health sciencesRare DiseasesInternal medicineGenetic variationmedicineGeneticsHumansGenetic Predisposition to DiseasePolymorphismAlleles030304 developmental biologyAutoimmune diseasegenome-wide association studybusiness.industryMultiple sclerosisRisk FactorArthritisInflammatory and immune systemHuman Genomemedicine.diseaseLymphomaBrain Disordersmeta-analysisbusiness[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
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