0000000001320295

AUTHOR

Harald Grallert

showing 10 related works from this author

Network reconstruction for trans acting genetic loci using multi-omics data and prior information.

2022

Background: Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors…

Data Integrationeducation.field_of_studyComputer scienceScale (chemistry)Bayesian probabilityPopulationQuantitative Trait LociBiological databaseInferenceData Integration ; Machine Learning ; Multi-omics ; Network Inference ; Personalized Medicine ; Prior Information ; Simulation ; Systems BiologyComputational biologyQuantitative trait locusReplication (computing)Machine LearningPrior probabilityCohortGeneticsMolecular MedicineHumans:Medicine [Science]Gene Regulatory NetworkseducationTranscriptomeMolecular BiologyGenetics (clinical)Genome medicine
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Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

2016

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were…

Male0301 basic medicinediabetes geneEndocrinology Diabetes and MetabolismGenome-wide association studyKidneyGLOMERULAR-FILTRATION-RATECathepsin CGene Knockout TechniquescubilinSettore MED/14 - NEFROLOGIADiabetic NephropathiesMODULATES PROTEINURIAddc:616HERITABILITYDiabetesGenetics/Genomes/Proteomics/MetabolomicsMiddle AgedRISK POPULATION COHORTS3. Good healthINSIGHTSKidney TubulesFemaleSulfotransferasesmedicine.symptomRAB38AdultEXPRESSIONmedicine.medical_specialtyRenal functionReceptors Cell Surface610 Medicine & healthSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotidealbuminuriaDiabetes Mellitus Experimental03 medical and health sciencesDiabetes mellitusInternal medicineInternal MedicinemedicineAnimalsHumansGenetic Predisposition to DiseaseAgedMORTALITYKIDNEY-DISEASEmedicine.diseaseCubilinRatsMinor allele frequency030104 developmental biologyEndocrinologyDiabetes Mellitus Type 2rab GTP-Binding ProteinsCOLLABORATIVE METAANALYSISAlbuminuria570 Life sciences; biologyalbuminuria diabetes cubilinGenome-Wide Association StudyKidney disease
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Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

2018

International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…

0301 basic medicineMaleNetherlands Twin Register (NTR)Bipolar DisorderLD SCORE REGRESSION[SDV]Life Sciences [q-bio]Genome-wide association study[SDV.GEN] Life Sciences [q-bio]/GeneticsBody Mass Indexinflammatory disorder80 and overWIDE ASSOCIATIONEPIDEMIOLOGYta318International HapMap ProjectChildGenetics (clinical)2. Zero hungerGeneticsGenetics & HeredityAged 80 and over[SDV.MHEP] Life Sciences [q-bio]/Human health and pathologyC-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biologysystem biologyDEPICTMendelian Randomization Analysis11 Medical And Health SciencesMiddle AgedC-reactive protein; coronary artery disease; DEPICT; genome-wide association study; inflammation; inflammatory disorders; Mendelian randomization; schizophrenia; system biology; Adolescent; Adult; Aged; Aged 80 and over; Biomarkers; Bipolar Disorder; Body Mass Index; C-Reactive Protein; Child; Female; Genetic Loci; Genome-Wide Association Study; Humans; Inflammation; Liver; Male; Mendelian Randomization Analysis; Metabolic Networks and Pathways; Middle Aged; Schizophrenia; Young Adult3. Good health[SDV] Life Sciences [q-bio]LiverMedical geneticsBiomarker (medicine)/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleinflammatory disordersLife Sciences & BiomedicineMetabolic Networks and Pathwayscoronary artery diseaseHumanAdultmedicine.medical_specialtyAdolescentCHARGE Inflammation Working GroupC-reactive protein ; DEPICT ; Mendelian randomization ; coronary artery disease ; genome-wide association study ; inflammation ; inflammatory disorders ; schizophrenia ; system biologyBiologyIMMUNITYta3111ArticleC-reactive protein03 medical and health sciencesYoung AdultSDG 3 - Good Health and Well-beingMendelian randomizationGeneticsmedicine/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_Mendelian randomizationHumansCORONARY-HEART-DISEASEMendelian Randomization Analysi1000 Genomes ProjectMETAANALYSISGenetic associationAged[SDV.GEN]Life Sciences [q-bio]/GeneticsScience & Technologygenome-wide association studyta1184Metabolic Networks and PathwayBiomarkerINSTRUMENTS06 Biological SciencesMendelian Randomization Analysisschizophrenia030104 developmental biologyGenetic LociinflammationC-reactive protein; DEPICT; Mendelian randomization; coronary artery disease; genome-wide association study; inflammation; inflammatory disorders; schizophrenia; system biology[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyBiomarkersLifeLines Cohort Study
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Maternal and fetal genetic contribution to gestational weight gain

2018

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspri…

0301 basic medicineAmniotic fluidEpidemiologyEndocrinology Diabetes and MetabolismEmbaràsMedicine (miscellaneous)Genome-wide association studyBLOOD-PRESSUREType 2 diabetes030204 cardiovascular system & hematology/dk/atira/pure/core/keywords/icepCOMMON SNPSGenètica mèdica0302 clinical medicinePregnancyWeight managementOFFSPRING ADIPOSITYMass index11 Medical and Health Sciences2. Zero hunger0303 health sciencesNutrition and DieteticsObstetricsHERITABILITYMedical geneticsta3141ASSOCIATIONGestational Weight Gainddc:3. Good healthGestational diabetesCHILDREN ALSPACmedicine.anatomical_structurePREGNANCYOBESITYMENDELIAN RANDOMIZATIONGestationOriginal ArticleFemaleICEPmedicine.symptomLife Sciences & Biomedicine13 EducationTRAITSmedicine.medical_specialtyOffspringBirth weightPes corporalDevelopmentBiology03 medical and health sciencesEndocrinology & MetabolismFetusPlacentaInternal medicinemedicineJournal ArticleHumans030304 developmental biologyFetusPregnancyScience & TechnologyNutrition & Dieteticsbusiness.industryta3121Body weightmedicine.diseaseta3123BIRTH-WEIGHTBODY-MASS INDEX030104 developmental biologyEndocrinologybusinessBody mass indexWeight gainHUMAN HEIGHTGenome-Wide Association Study
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

2016

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

0301 basic medicineNephrologyGenetics and Molecular Biology (all)estimated glomerular filtration rateestimated glomerular filtration rate chronic kidney disease genetic determinantsGeneral Physics and AstronomyKidney developmentGenome-wide association studyBiochemistrySettore MED/14 - NEFROLOGIARenal InsufficiencyChronicGeneticsAGEN Consortiumddc:616education.field_of_studyKidneyStage renal-diseaseMultidisciplinaryGenome-wide associationCHARGe-Heart Failure GroupGene Expression Regulation; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic; Genetic Predisposition to Disease; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)QChemistry (all)MetaanalysisGene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic/geneticsBiological sciencesSerum creatininemedicine.anatomical_structureEfficientRonyons -- FisiologiaHypertensionICBP ConsortiumTransmembrane transporter activitygenetic association loci kidney functionCARDIOGRAMHumanmedicine.medical_specialtyGenotypeSciencePopulationRenal functionECHOGen ConsortiumReplicationBiologyEnvironmentResearch SupportGeneral Biochemistry Genetics and Molecular BiologyN.I.H.genetic determinants03 medical and health sciencesPhysics and Astronomy (all)GENOME-WIDE ASSOCIATION ; FALSE DISCOVERY RATES ; STAGE RENAL-DISEASE ; SERUM CREATININE ; METAANALYSIS ; VARIANTS ; INDIVIDUALS ; POPULATION ; RISK ; HYPERTENSIONKidney functionResearch Support N.I.H. ExtramuralInternal medicineMD MultidisciplinarymedicineGeneticsJournal ArticleHumanseGFRcrea; eGFRcysGenetic Predisposition to Diseaseddc:610GenetikRenal Insufficiency ChronicMortalityeducationddc:613Biochemistry Genetics and Molecular Biology (all)urogenital systemIndividualsExtramuralGeneral Chemistryta3121medicine.diseaseR1030104 developmental biologyGene Expression RegulationBiochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)570 Life sciences; biologyGenèticachronic kidney diseaseKidney diseaseGenome-Wide Association StudyMeta-Analysis
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Analyzing Illumina Gene Expression Microarray Data from Different Tissues: Methodological Aspects of Data Analysis in the MetaXpress Consortium

2012

Microarray profiling of gene expression is widely applied in molecular biology and functional genomics. Experimental and technical variations make meta-analysis of different studies challenging. In a total of 3358 samples, all from German population-based cohorts, we investigated the effect of data preprocessing and the variability due to sample processing in whole blood cell and blood monocyte gene expression data, measured on the Illumina HumanHT-12 v3 BeadChip array. Gene expression signal intensities were similar after applying the log(2) or the variance-stabilizing transformation. In all cohorts, the first principal component (PC) explained more than 95% of the total variation. Technic…

MicroarraysArray ProcessingClinical Research DesignScienceGene ExpressionSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideMolecular Genetics03 medical and health sciencesEngineering0302 clinical medicineGenome Analysis ToolsGermanyWhite blood cellGene expressionGenome-Wide Association StudiesGeneticsmedicineHumansGenome SequencingStatistical MethodsBiologyOligonucleotide Array Sequence Analysis030304 developmental biologyWhole bloodGenetics0303 health sciencesMultidisciplinaryGene Expression ProfilingQRComputational BiologyReproducibility of ResultsHuman GeneticsGenomicsGene expression profilingMinor allele frequencymedicine.anatomical_structure030220 oncology & carcinogenesisSignal ProcessingMedicineRNA extractionFunctional genomicsResearch ArticlePLoS ONE
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Genome-wide association analysis identifies six new loci associated with forced vital capacity

2014

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P &lt;5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispani…

SpirometryLung DiseasesVital capacityQuantitative Trait LociVital CapacityGenome-wide association studyBiologyPolymorphism Single NucleotideArticleDISEASEPulmonary function testingCohort StudiesFEV1/FVC ratioIdiopathic pulmonary fibrosisSDG 3 - Good Health and Well-beingMeta-Analysis as TopicForced Expiratory VolumeDatabases GeneticGeneticsmedicineHumansRestrictive lung diseaseLung volumesGenetic Predisposition to Diseaselung; spriometry; SNP; geneGENE-EXPRESSIONGeneticsmedicine.diagnostic_testGenome HumanHERITABILITYHEALTHY TWINMORTALITYta3141respiratory systemmedicine.diseasePrognosis3. Good healthRespiratory Function Testsrespiratory tract diseasesFAMILYLUNG-FUNCTIONGenetic LociSpirometryImmunologyCELLSIDIOPATHIC PULMONARY-FIBROSISTRAITSFollow-Up StudiesGenome-Wide Association StudyNature Genetics
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Comparison of genetic risk prediction models to improve prediction of coronary heart disease in two large cohorts of the MONICA/KORA study

2021

Abstract It is still unclear how genetic information, provided as single‐nucleotide polymorphisms (SNPs), can be most effectively integrated into risk prediction models for coronary heart disease (CHD) to add significant predictive value beyond clinical risk models. For the present study, a population‐based case‐cohort was used as a trainingset (451 incident cases, 1488 noncases) and an independent cohort as testset (160 incident cases, 2749 noncases). The following strategies to quantify genetic information were compared: A weighted genetic risk score including Metabochip SNPs associated with CHD in the literature (GRSMetabo); selection of the most predictive SNPs among these literature‐co…

Oncologymedicine.medical_specialtyEpidemiologyFramingham Risk Score ; Metabochip ; Coronary Heart Disease ; Genomic Risk Prediction ; Priority-lassoPopulationCoronary DiseaseSingle-nucleotide polymorphismKoronare HerzkrankheitPolymorphism Single NucleotideRisk AssessmentCohort Studies03 medical and health sciencesRisk FactorsInternal medicinemedicineHumansgenomic risk predictionddc:610coronary heart diseaseMetabochipGenetikeducationGenotypingGenetics (clinical)030304 developmental biologypriority‐Lasso0303 health scienceseducation.field_of_studyFramingham Risk ScoreModels GeneticProportional hazards modelbusiness.industry030305 genetics & heredityGenomicsConfidence intervalddc:Coronary disease; GeneticsRisk factorsCohortFramingham risk scorebusinessDDC 610 / Medicine &amp; healthPredictive modelling
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Additional file 1 of Network reconstruction for trans acting genetic loci using multi-omics data and prior information

2022

Additional file 1 Supplementary material, supporting figures and tables.

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Additional file 2 of Network reconstruction for trans acting genetic loci using multi-omics data and prior information

2022

Additional file 2 Supplementary tables, large supporting tables with table titles as tabs.

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