Featured Publications
Susceptibility loci for intracranial aneurysm in European and Japanese populations
Bilguvar K, Yasuno K, Niemelä M, Ruigrok YM, von und zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaál E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Öhman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jääskeläinen JE, Palotie A, Inoue I, Lifton RP, Günel M. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nature Genetics 2008, 40: 1472-1477. PMID: 18997786, PMCID: PMC2682433, DOI: 10.1038/ng.240.Peer-Reviewed Original ResearchGenome-wide association study of intracranial aneurysm identifies three new risk loci
Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, Simon M, Krex D, Arlier Z, Nayak N, Ruigrok YM, Niemelä M, Tajima A, von und zu Fraunberg M, Dóczi T, Wirjatijasa F, Hata A, Blasco J, Oszvald A, Kasuya H, Zilani G, Schoch B, Singh P, Stüer C, Risselada R, Beck J, Sola T, Ricciardi F, Aromaa A, Illig T, Schreiber S, van Duijn CM, van den Berg LH, Perret C, Proust C, Roder C, Ozturk AK, Gaál E, Berg D, Geisen C, Friedrich CM, Summers P, Frangi AF, State MW, Wichmann HE, Breteler MM, Wijmenga C, Mane S, Peltonen L, Elio V, Sturkenboom MC, Lawford P, Byrne J, Macho J, Sandalcioglu EI, Meyer B, Raabe A, Steinmetz H, Rüfenacht D, Jääskeläinen JE, Hernesniemi J, Rinkel GJ, Zembutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Günel M. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nature Genetics 2010, 42: 420-425. PMID: 20364137, PMCID: PMC2861730, DOI: 10.1038/ng.563.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell ProliferationCohort StudiesEuropeFemaleGenome-Wide Association StudyGenotypeHemorrhageHumansIntracranial AneurysmJapanMaleModels, GeneticOdds RatioPolymorphism, Single NucleotideCommon variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk
Yasuno K, Bakırcıoğlu M, Low SK, Bilgüvar K, Gaál E, Ruigrok YM, Niemelä M, Hata A, Bijlenga P, Kasuya H, Jääskeläinen JE, Krex D, Auburger G, Simon M, Krischek B, Ozturk AK, Mane S, Rinkel GJ, Steinmetz H, Hernesniemi J, Schaller K, Zembutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Günel M. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 19707-19712. PMID: 22106312, PMCID: PMC3241810, DOI: 10.1073/pnas.1117137108.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesDiscovery cohortDisease-related lociReplication cohortSignificant associationEndothelin receptor type AGenomic regionsChromosome 12q22Genetic evidenceIndependent Japanese cohortsIntracranial aneurysm formationRisk lociA geneEvidence of associationAssociation studiesEndothelin pathwayAneurysm formationEndothelin signalingCardiovascular disordersJapanese cohortLociCohortCommon variantsGenetic factorsTreatment of IA
2021
Genetically Determined Low‐Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage
Acosta JN, Both CP, Szejko N, Leasure AC, Abdelhakim S, Torres‐Lopez V, Brown SC, Matouk CC, Gunel M, Sheth KN, Falcone GJ. Genetically Determined Low‐Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage. Annals Of Neurology 2021, 91: 145-149. PMID: 34709661, DOI: 10.1002/ana.26250.Peer-Reviewed Original ResearchMeSH KeywordsCholesterol, LDLHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideSubarachnoid Hemorrhage
2020
Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage
Falcone GJ, Kirsch E, Acosta JN, Noche RB, Leasure A, Marini S, Chung J, Selim M, Meschia JF, Brown DL, Worrall BB, Tirschwell DL, Jagiella JM, Schmidt H, Jimenez‐Conde J, Fernandez‐Cadenas I, Lindgren A, Slowik A, Gill D, Holmes M, Phuah C, Petersen NH, Matouk CN, Gunel M, Sansing L, Bennett D, Chen Z, Sun LL, Clarke R, Walters RG, Gill TM, Biffi A, Kathiresan S, Langefeld CD, Woo D, Rosand J, Sheth KN, Anderson CD, Consortium F. Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage. Annals Of Neurology 2020, 88: 56-66. PMID: 32277781, PMCID: PMC7523882, DOI: 10.1002/ana.25740.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overCerebral HemorrhageCholesterol, HDLCholesterol, LDLFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideTriglyceridesConceptsIntracerebral hemorrhagePolygenic risk scoresLDL cholesterolLower riskTotal cholesterolICH riskLow-density lipoprotein cholesterol levelsRisk of ICHLipoprotein cholesterol levelsPotential causal roleMendelian randomization analysisAnn NeurolLDL levelsCholesterol levelsICH casesObservational studySD increaseSignificant single nucleotide polymorphismsRisk scoreSignificant associationCholesterolMR analysisInverse correlationRandomization analysisSingle nucleotide polymorphisms
2018
MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome)
Rad A, Altunoglu U, Miller R, Maroofian R, James KN, Çağlayan AO, Najafi M, Stanley V, Boustany RM, Yeşil G, Sahebzamani A, Ercan-Sencicek G, Saeidi K, Wu K, Bauer P, Bakey Z, Gleeson JG, Hauser N, Gunel M, Kayserili H, Schmidts M. MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome). Journal Of Medical Genetics 2018, 56: 332. PMID: 30487245, PMCID: PMC6581149, DOI: 10.1136/jmedgenet-2018-105623.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleBrainChildChild, PreschoolConsanguinityExome SequencingFaciesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHomeodomain ProteinsHomozygoteHumansInfantLoss of Function MutationMagnetic Resonance ImagingMaleModels, MolecularNeurodevelopmental DisordersPedigreePhenotypePolymorphism, Single NucleotideProtein ConformationSyndromeConceptsScrotal agenesisCerebellar hypoplasiaCharacteristic facial gestaltHomozygous truncating variantConsanguineous familyUnrelated consanguineous familiesOphthalmological anomaliesSyndromic neurodevelopmental disorderCardinal featuresCerebello-oculoCorneal dystrophyLabioscrotal foldsTruncating variantsFunction variantsFacial gestaltExome sequencingSyndromeSimilar phenotypic featuresGenetic causeFacial dysmorphismNeurodevelopmental disordersMissense variantsVariable microcephalyNeurodevelopmental syndromeAffected individuals
2016
IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation
Oktay Y, Ülgen E, Can Ö, Akyerli CB, Yüksel Ş, Erdemgil Y, Durası İ, Henegariu OI, Nanni EP, Selevsek N, Grossmann J, Erson-Omay EZ, Bai H, Gupta M, Lee W, Turcan Ş, Özpınar A, Huse JT, Sav MA, Flanagan A, Günel M, Sezerman OU, Yakıcıer MC, Pamir MN, Özduman K. IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation. Scientific Reports 2016, 6: 27569. PMID: 27282637, PMCID: PMC4901315, DOI: 10.1038/srep27569.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAllelesBiomarkers, TumorFemaleGene Expression Regulation, NeoplasticGenetic Association StudiesGenetic Predisposition to DiseaseGliomaHumansIsocitrate DehydrogenaseKaplan-Meier EstimateMaleMiddle AgedMutationNeoplasm GradingNeoplasm ProteinsPolymorphism, Single NucleotideProteomicsProto-Oncogene Proteins c-mycSequence Analysis, RNAConceptsCase-control studySubtype-specific differencesMYC deregulationSystemic cancerCNS tumorsHealthy controlsAllele carriersLC-MS/MS comparisonModulatory effectsCartilaginous tumorsControl studyPositive modulationUnderlying causeGliomasIDH-mutant gliomasObserved associationsGlioma developmentSomatic mutationsDriver genesAssociationRs55705857RNA sequencingMolecular mechanismsSpecific associationMYC promoter
2013
Mutations in CSPP1 Lead to Classical Joubert Syndrome
Akizu N, Silhavy JL, Rosti RO, Scott E, Fenstermaker AG, Schroth J, Zaki MS, Sanchez H, Gupta N, Kabra M, Kara M, Ben-Omran T, Rosti B, Guemez-Gamboa A, Spencer E, Pan R, Cai N, Abdellateef M, Gabriel S, Halbritter J, Hildebrandt F, van Bokhoven H, Gunel M, Gleeson JG. Mutations in CSPP1 Lead to Classical Joubert Syndrome. American Journal Of Human Genetics 2013, 94: 80-86. PMID: 24360807, PMCID: PMC3882909, DOI: 10.1016/j.ajhg.2013.11.015.Peer-Reviewed Original ResearchConceptsJoubert syndromeDistinctive mid-hindbrain malformationMid-hindbrain malformationPrimary cilia dysfunctionPrimary ciliaKidney diseaseLarge cohortVariable involvementRelated disordersHuman neurogenesisNeural tissueProtein levelsAffected individualsSyndromeCilia dysfunctionCohortNeural-specific functionsCausative mutationsMutationsNull mutationCSPP1IndividualsCiliaDysfunctionJSRD
2012
Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure
Gaál EI, Salo P, Kristiansson K, Rehnström K, Kettunen J, Sarin AP, Niemelä M, Jula A, Raitakari OT, Lehtimäki T, Eriksson JG, Widen E, Günel M, Kurki M, von und zu Fraunberg M, Jääskeläinen JE, Hernesniemi J, Järvelin MR, Pouta A, , Newton-Cheh C, Salomaa V, Palotie A, Perola M. Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure. PLOS Genetics 2012, 8: e1002563. PMID: 22438818, PMCID: PMC3305343, DOI: 10.1371/journal.pgen.1002563.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood PressureChromosomes, Human, Pair 5Cohort StudiesFemaleFinlandGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIntracranial AneurysmMaleMiddle AgedMuscle ProteinsMyocytes, Smooth MusclePolymorphism, Single NucleotideRisk FactorsTranscription FactorsZinc FingersConceptsSystolic blood pressureBlood pressureSystolic BPRisk factorsIntracranial aneurysmsElevated systolic blood pressurePopulation-based Finnish cohortsDiastolic blood pressureHigher systolic BPMean arterial pressureTraditional risk factorsVascular smooth muscle cellsStrong risk factorCommon risk factorsQuantitative outcome variablesVascular wall structureSmooth muscle cellsGenome-wide association studiesArterial pressureCerebral arteryPulse pressureFinnish cohortComplex diseasesMuscle cellsRisk alleles
2011
Genome-wide association study identifies susceptibility loci for IgA nephropathy
Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nature Genetics 2011, 43: 321-327. PMID: 21399633, PMCID: PMC3412515, DOI: 10.1038/ng.787.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAsian PeopleBlood ProteinsCase-Control StudiesChromosomes, Human, Pair 1Chromosomes, Human, Pair 22Cohort StudiesComplement C3b Inactivator ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGlomerulonephritis, IGAHLA AntigensHumansMajor Histocompatibility ComplexMalePolymorphism, Single NucleotideRisk FactorsSelection, GeneticWhite PeopleYoung Adult
2009
The syndrome of pachygyria, mental retardation, and arachnoid cysts maps to 11p15
Bilguvar K, Ozturk AK, Bayrakli F, Guzel A, DiLuna ML, Bayri Y, Tatli M, Tekes S, Arlier Z, Yasuno K, Mason CE, Lifton RP, State MW, Gunel M. The syndrome of pachygyria, mental retardation, and arachnoid cysts maps to 11p15. American Journal Of Medical Genetics Part A 2009, 149A: 2569-2572. PMID: 19876906, DOI: 10.1002/ajmg.a.33063.Peer-Reviewed Original ResearchAbnormalities, MultipleArachnoid CystsBlood Specimen CollectionChromosome MappingChromosomes, Human, Pair 11DNADNA Copy Number VariationsFamilyFemaleGenome, HumanGenome-Wide Association StudyGenotypeHomozygoteHumansIntellectual DisabilityLissencephalyLod ScoreMalePedigreePhenotypePolymorphism, Single NucleotideSyndrome
2008
Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population
Tüysüz B, Bayrakli F, DiLuna ML, Bilguvar K, Bayri Y, Yalcinkaya C, Bursali A, Ozdamar E, Korkmaz B, Mason CE, Ozturk AK, Lifton RP, State MW, Gunel M. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population. Neurogenetics 2008, 9: 119-125. PMID: 18322713, DOI: 10.1007/s10048-008-0121-9.Peer-Reviewed Original ResearchConceptsNeurotrophic tyrosine kinase receptor type 1Autonomic neuropathy type IVHSAN IVHereditary sensoryNTRK1 geneTurkish populationFounder mutationType IVReceptor type 1Nerve growth factorSplice site mutationAutosomal recessive disorderCongenital insensitivityNovel frameshift mutationSame splice site mutationNTRK1 mutationsNoxious stimuliType 1Motor developmentSweat glandsGrowth factorNovel nonsense mutationRecessive disorderSpectrum of mutationsAnhidrosis
2007
Rapid identification of disease‐causing mutations using copy number analysis within linkage intervals
Bayrakli F, Bilguvar K, Mason CE, DiLuna ML, Bayri Y, Gungor L, Terzi M, Mane SM, Lifton RP, State MW, Gunel M. Rapid identification of disease‐causing mutations using copy number analysis within linkage intervals. Human Mutation 2007, 28: 1236-1240. PMID: 17676595, DOI: 10.1002/humu.20592.Peer-Reviewed Original ResearchMeSH KeywordsGene DosageGenes, RecessiveGenetic LinkageGenetic Predisposition to DiseaseGenetic TestingHumansMutationParkinsonian DisordersPolymorphism, Single NucleotideUbiquitin-Protein LigasesConceptsCopy number variationsComparative genome hybridization arraysParametric linkage analysisArray-based detectionCopy number analysisDisease-causing mutationsGenome rearrangementsLinkage intervalRapid identificationAutosomal recessive parkinsonismFunctional mutationsLinkage analysisNumber variationsRecessive parkinsonismHybridization arraysPARK2 gene
2004
Mapping a Mendelian Form of Intracranial Aneurysm to 1p34.3-p36.13
Nahed BV, Seker A, Guclu B, Ozturk AK, Finberg K, Hawkins AA, DiLuna ML, State M, Lifton RP, Gunel M. Mapping a Mendelian Form of Intracranial Aneurysm to 1p34.3-p36.13. American Journal Of Human Genetics 2004, 76: 172-179. PMID: 15540160, PMCID: PMC1196421, DOI: 10.1086/426953.Peer-Reviewed Original ResearchConceptsMendelian formsSimple tandem repeatsIdentification of pathwaysHigh penetranceSingle geneUnderlying genesSingle nucleotide polymorphismsSingle locusTandem repeatsCandidate intervalGenomewide studiesDisease locusAnalysis of linkageLOD scoreLociRare familiesSignificant linkageRelative pairsGenesDominant traitEnvironmental factorsLarge kindredPenetranceRepeatsTraits