0000000000381011

AUTHOR

Katrin Männik

showing 3 related works from this author

Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants

2019

Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. Results: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with thei…

MaleParents0301 basic medicineProbandNeuronalGenetic Carrier Screening16p11.2 deletion030105 genetics & heredityCognitionFamily historyNeural Cell Adhesion MoleculesGenetics (clinical)Exome sequencingSequence DeletionGeneticsGenetic Carrier ScreeningPhenotypePenetrancePedigreePhenotypeAutistic Disorder/genetics; Autistic Disorder/physiopathology; Cell Adhesion Molecules Neuronal/genetics; Chromosomes Human Pair 16/genetics; Cognition/physiology; DNA Copy Number Variations/genetics; Female; Gene Expression Regulation/genetics; Genetic Background; Genetic Carrier Screening; Humans; Male; Methyltransferases/genetics; Nerve Tissue Proteins/genetics; Parents; Pedigree; Phenotype; Proteins/genetics; Sequence Deletion/genetics; Siblings; 16p11.2 deletion; CNV; autism; modifier; phenotypic variabilityFemaleGenetic BackgroundHumanDNA Copy Number VariationsCell Adhesion Molecules NeuronalCNVautismNerve Tissue ProteinsBiologyChromosomesArticle03 medical and health sciencesmental disordersmedicineHumansAutistic DisorderBiologyGenemodifierPair 16SiblingsCalcium-Binding ProteinsProteinsMethyltransferasesmedicine.disease16p11.2 deletion; autism; CNV; modifier; phenotypic variability; Genetics (clinical)Cytoskeletal Proteins030104 developmental biologyGene Expression Regulation[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsAutismphenotypic variabilityHuman medicine16p11.2 deletion; autism; CNV; modifier; phenotypic variability; Autistic Disorder; Cell Adhesion Molecules Neuronal; Chromosomes Human Pair 16; Cognition; DNA Copy Number Variations; Female; Gene Expression Regulation; Genetic Background; Humans; Male; Methyltransferases; Nerve Tissue Proteins; Parents; Pedigree; Phenotype; Proteins; Sequence Deletion; Siblings; Genetic Carrier ScreeningCell Adhesion MoleculesChromosomes Human Pair 16Transcription FactorsGenetics in Medicine
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

2020

AbstractEating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], …

Netherlands Twin Register (NTR)Alcoholism/geneticsSchizophrenia/genetics[SDV]Life Sciences [q-bio][SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental healthMedizinMedicine (miscellaneous)Genome-wide association studyAlcohol use disorderAnorexia nervosaLinkage Disequilibriumddc:616.89[SCCO]Cognitive science0302 clinical medicineRisk FactorsTobacco Use Disorder/geneticsSubstance-Related Disorders/genetics0303 health sciences[SDV.MHEP] Life Sciences [q-bio]/Human health and pathologyFactors de risc en les malaltiesBulimia nervosaFeeding and Eating Disorders/geneticseating disorders; genetic correlation; substance useTobacco Use Disordergenetic correlation3. Good healthFenotip[SDV] Life Sciences [q-bio]Psychiatry and Mental healthAlcoholismEating disordersPhenotypeSchizophreniaDrinking of alcoholic beverageseating disorderConsum d'alcoholMajor depressive disorder/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingmedicine.symptomDepressive Disorder Major/geneticseating disorders genetic correlation substance useClinical psychologySubstance abuseRisk factors in diseasesSubstance-Related Disorderssubstance useeating disordersPolymorphism Single NucleotideArticleFeeding and Eating Disorders03 medical and health sciencesSDG 3 - Good Health and Well-beingmental disorders/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_GeneticsmedicineHumansTrastorns de la conducta alimentària030304 developmental biologyGenetic associationPharmacologyeating disorders ; genetic correlation ; substance useDepressive Disorder MajorBinge eatingbusiness.industry[SCCO.NEUR]Cognitive science/Neuroscience[SCCO.NEUR] Cognitive science/Neurosciencesubstance use.[SCCO] Cognitive sciencemedicine.diseaseComorbidityTwin study030227 psychiatryAbús de substàncies[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental healthSchizophreniabusinessGenètica030217 neurology & neurosurgery[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyGenome-Wide Association Study
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Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders

2018

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to …

GeneticsProband0303 health sciencesCandidate geneMutationGenetic heterogeneityDiseaseBiologymedicine.diseasemedicine.disease_cause03 medical and health sciences0302 clinical medicinemedicineAutismExpressivity (genetics)Family history030217 neurology & neurosurgery030304 developmental biology
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