6533b86efe1ef96bd12cca7d

RESEARCH PRODUCT

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Peter P. ZandiLisa JonesAartjan T.f. BeekmanChristine FraserAndreas J. ForstnerNese DirekMark LathropJesper KroghMerete NordentoftBradley T. WebbYihan LiMichael BauerQingqin S. LiDaniel J. SmithCarsten HornRobert C. ThompsonRené BreuerEli A. StahlDavid A. CollierRichard WilliamsonDorret BoomsmaCéline S. ReinboldLaura J. ScottManolis KogevinasJacob LawrenceCaroline HaywardNicholas J. SchorkPenelope A. LindWade H. BerrettiniJohn B. VincentToni-kim ClarkeHenry VoelzkeStacy SteinbergHreinn StefanssonDean F. MackinnonThorgeir E. ThorgeirssonNiamh MullinsEsben AgerboRudolf UherChristina M. HultmanPamela A. F. MaddenEva C. SchulteMatthew FlickingerSebastian ZöllnerKenneth S. KendlerUrban ÖSbyEnrique CastelaoMichael John OwenColm O'dushlaineJens TreutleinJoanna HauserMarkus M. NoethenErin N. SmithJames MckaySandra Van Der AuweraErin C. DunnSteven P. HamiltonMartin SchallingHelmut VedderKatherine Gordon-smithFabio RivasMatthias NauckJames B. PotashMorten MattingsdalLing ShenTim B. BigdeliKimberly ChambertVolker AroltDaniel L. KollerAnnelie Nordin AdolfssonNa CaiNicholas G. MartinCarlos N. PatoGeorg HomuthJonas Bybjerg-grauholmAlexander TeumerWesley K. ThompsonHamel PatelJian YangMargit BurmeisterFrank BellivierJodie N. PainterEnda M. ByrneEnda M. ByrneMargarita RiveraNicholas John CraddockTatiana ForoudShaun PurcellPaul D. ShillingDavid CraigVanessa Kiyomi OtaMichael BoehnkeDevin AbsherStéphane JamainAnne FarmerYunpeng WangOle MorsWilliam A. ScheftnerJack D. BarchasRobert MaierStanley J. WatsonAllan H. YoungBaptiste Couvy-duchesneJakob GroveRick JansenJohn P. RiceGerome BreenGerome BreenEske M. DerksIngrid MelleTiffany A. GreenwoodManuel MattheisenBernard NgEdward M. ScolnickStefan KloiberLili MilaniYuri MilaneschiFermín MayoralEngilbert SigurdssonSarah E. MedlandWolfgang MaierAlan F. SchatzbergMyrna M. WeissmanJun LiJohn R. KelsoeEric JorgensonGrant C.b. SinnamonPreben Bo MortensenJana StrohmaierWilliam ByerleyMichel G. NivardRichard M. MyersEvelin MihailovGustavo TureckiBenjamin S. PickardIan J. DearyBernhard T. BauneMarian L. HamshereStephanie H. WittPatrick F. SullivanJennifer L. MoranFarnush Farhadi Hassan KiadehCathryn M. LewisSrdjan DjurovicIan B. HickieHans J. GrabeHelena GasparFrancis J. McmahonCatherine SchaeferGuy A. RouleauSandra MeierDerek W. MorrisTõnu EskoWouter J. PeyrotMarkus SchwarzSilviu-alin BacanuAdam WrightMelvin G. McinnisElaine K. GreenDouglas M. RuderferDanielle PosthumaFranziska DegenhardtPer QvistHenriette N. ButtenschønJolanta LissowskaStephan RipkeNicholas BassGiorgio PistisEmma M. QuinnShantel WeinsheimerHoward J. EdenbergSintia Iole BelangeroCharles CurtisCharles CurtisAshley R. WinslowTracy M. AirJohannes H. SmitIsaac S. KohaneWei XuPamela B. MahonNeonila Szeszenia-dabrowskaGonneke WillemsenIvan NikolovSven CichonGregory E. CrawfordDavid M. HougaardE.j.c. De GeusKlaus BergerEvaristus A. NwuliaFernando S. GoesPablo CervantesUdo DannlowskiRolf AdolfssonThomas G. SchulzeBruno EtainMark J. AdamsThomas HansenHugh GurlingFan Guo MengJudith A. BadnerJulien BryoisMateus Jose Abdalla DinizRodrigo A. BressanRadhika KandaswamyJosef FrankI. Nicol FerrierBertram Mueller-myhsokManuel A. R. FerreiraMarion LeboyerFutao ZhangValentina MoskvinaPatrik K. E. MagnussonLaura M. HuckinsDouglas BlackwoodMichael GillJianxin ShiDale R. NyholtNancy L. PedersenAndré G. UitterlindenHenning TiemeierVassily TrubetskoyScott D. GordonIan JonesGrant W. MontgomeryMartin PreisigCristiana CruceanuSara A. PacigaLena BacklundAbdel AbdellaouiAndres MetspaluGunnar MorkenMarcus IsingSascha B. FischerLilijana OrucSian CaesarSarah Kittel-schneiderThalia C. EleyVihra MilanovaThomas WergeAndrew HeathKatherine E. TanseyThomas W. MuehleisenJane H. ChristensenChunyu LiuMikael LandénDouglas F. LevinsonJulia KraftJuergen WellmannJonathan R. ColemanPeng ZhangGlyn LewisHenning TeismannHamdi MbarekCarsten Bøcker PedersenSzabolcs SzelingerAlexander ViktorinPaul BrennanBrenda W.j.h. PenninxMaciej TrzaskowskiYang WuKatharina DomschkeJohn StraussHilary K. FinucaneDetelina GrozevaPeter HolmansSaira Saeed MirzaOle A. AndreassenJohn I. NurnbergerLynsey S HallTill F. M. AndlauerSara MostafaviAndreas ReifJoanna M. BiernackaChristine Søholm HansenHualin S. XiStephen NewhouseWilliam E. BunneyAndrew M. McintoshAnna MaaserEnrico DomeniciStanley ShynGail DaviesWarren W. KretzschmarSimone De JongSimone De JongLucía Colodro-condePippa A. ThomsonFrancis M. MondimoreMartin HautzingerCinnamon S. BlossFabian StreitJames L. KennedyErik PetterssonPeter M. VisscherValentina Escott-priceDonald J. MacintyreJohannes SchumacherKevin A. McgheeDivya MehtaNaomi R. WrayNaomi R. WrayRobert A. SchoeversJohn A. RiceJordan W. SmollerAnders D. BørglumSusanne LucaeJorge A. QuirozDaniel UmbrichtJouke-jan HottengaKari StefanssonMarcella RietschelZoltán KutalikSarah E. BergenPaul F. O'reillyAmanda DobbynMichael Conlon O'donovanFalk W. LohoffCaroline M. NievergeltDavid J. PorteousMatthew TraylorBrien P. RileyRoy H. PerlisJ. Raymond DepauloMartin AldaJames A. KnowlesCristiano NotoKeith MatthewsMark A. FryePatrick J. McgrathRoseann E. PetersonDavid St ClairRoel A. OphoffWilliam CoryellPeter McguffinAndiara Calado Saloma RodriguesElliot S. GershonConor V. DolanJanice M. FullertonWeihua GuanNiklas LångströmPamela SklarPaul LichtensteinPer HoffmannAry GadelhaAlan W. McleanAndrew McquillinPhilip B. MitchellHuda AkilPiotr M. CzerskiMichael SteffensHogni OskarssonSoumya RaychaudhuriMarcos L. SantoroElisabeth B. BinderChristel M. MiddeldorpJose G. ParaJurgen Del-faveroVishwajit L. NimgaonkarPeter R. SchofieldStefan HermsMarie Bækvad-hansenAndrea PfennigAlbert M. Van HemertJutta Kammerer-cierniochAdebayo AnjorinSara PacigaWilliam LawsonGeorge KirovAiden CorvinMaria Grigoroiu-serbanescuMarianne Giørtz PedersenJonathan MarchiniMarkus LeberMaria HipolitoLouise FrisénMargitta Borrmann-hassenbachAmanda Elkin

subject

Netherlands Twin Register (NTR)0301 basic medicineMajor Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics ConsortiumBipolar DisorderSAMPLEMedicine (miscellaneous)Pedigree chartDisease0302 clinical medicineSCHIZOPHRENIA2.1 Biological and endogenous factorsMedicineAetiologyANTICIPATIONlcsh:QH301-705.5Psychiatry0303 health sciencesDepressionASSOCIATIONSerious Mental IllnessPeer reviewMental HealthSchizophrenia/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingMajor depressive disorderGeneral Agricultural and Biological SciencesEngineering sciences. Technologymedicine.medical_specialtyContext (language use)ArticlePsykiatriGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesAGESDG 3 - Good Health and Well-beingddc:570Behavioral and Social Science/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_GeneticsPLINKGenetic TestingBipolar disorderPsychiatryBiology030304 developmental biologybusiness.industryPreventionHuman GenomeAssortative matingmedicine.diseaseBrain Disorders030104 developmental biologyMoodlcsh:Biology (General)Mood disordersAnticipation (genetics)ONSETHuman medicinebusiness030217 neurology & neurosurgery

description

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

yearjournalcountryeditionlanguage
2018-10-08
10.1038/s42003-018-0155-yhttps://hdl.handle.net/1956/19697