Age distributions per dataset

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2 Age distributions per dataset MAS LBC OATS PAFIP IDIVAL SHIP NCNG SHIP Trend UCLA NL BP HUBIN STROKEMRI Würzburg Tübingen HMS NESDA OCD VUmc Amsterdam T OCD Fukuoka FBIRN OCD VUmc Amsterdam.T TOP Osaka.T OCD Barcelona OCD London MüNC IMpACT OCD Kunming.T OCD Kyoto.T OCD Kyoto T OCD SU UMCU PAFIP IDIVAL TCD NUIG MCIC CIAM PAFIP IDIVAL OCD India T OCD India.T OCD SNU A OCD Kunming T Meth CT OCD Shangai BIL & GIN Osaka T OCD SNU C OCD SNU B CLiNG BIG.T QTIM BIG T BP Houston NeuroIMAGE OCD Zürich IMAGEN OCD AMC 0 0

3 SupplementaryTableS:DatasetdescriptionandMRimageacquisitiondetails.OntheleftcolumnarethereferencenumbersasusedinTableI,Figures,andSupplementaryMaterialS. Referencenumber Dataset Description Scanner(s) FreeSurferversion Tacquisitiondetails BIG.T BIGT TheBrainImagingGeneticsdatabase,splitbyscannerfieldstrength.A.T(Sonata;Avanto)Siemens. populationbasedsamplefromnijmegen,thenetherlands TheBrainImagingGeneticsdatabase,splitbyscannerfieldstrength.A T(Trio;TimTrio)Siemens. populationbasedsamplefromnijmegen,thenetherlands MRIdatainBIGwereacquiredwitheithera.TeslaSiemensSonataorAvantoscanneroraTeslaSiemensTrioorTimTrio scanner(erlangen,germany).giventhatimageswereacquiredduringseveralsmallerscalestudies,theparametersused wereslightvariationsofastandardtweightedthreedimensionalmagnetizationpreparedrapidgradientechosequence (MPRAGE;.0.0.0mmvoxelsize). MRIdatainBIGwereacquiredwitheithera.TeslaSiemensSonataorAvantoscanneroraTeslaSiemensTrioorTimTrio scanner(erlangen,germany).giventhatimageswereacquiredduringseveralsmallerscalestudies,theparametersused wereslightvariationsofastandardtweightedthreedimensionalmagnetizationpreparedrapidgradientechosequence (MPRAGE;.0.0.0mmvoxelsize). TheBrainimagingoflateralizationstudyatGrouped'Imagerie DTweightedsequence:DFFETFE;TR=ms;TE=.ms;flipangle= ;inversiontime=00ms;turbofieldecho BIL&GIN Neurofonctionnelle,asampleofadultparticipantsenrichedinleft T(Achieva)Philips. factor=;sensefactor=;matrixsize=xxmm;mmisotropicvoxelsize handers(%),frombordeaux,france(mazoyeretal.,) a)tweightedmpragescans:flipangle=,echotime(te)=.ms,repetitiontime(tr)=0ms,slicethickness=mm, matrix=x,numberofslices=. a)t(allegra)siemens();b).t(gyroscan AsubsetofhealthycontrolsfromtheSearchingforEndophenotypes b)tweightedspoiledgradientrecalled(spgr)scans:flipangle=,echotime(te)=ms,repetitiontime(tr)=ms,slice BPHouston Intera)Philips&c).T(GyroscanIntera). ofbipolardisordersstudy(bp) thickness=mm,matrix=x,numberofslices=. Philips c)tweightedsensedscans:flipangle=,echotime(te)=.ms,repetitiontime(tr)=ms,slicethickness=mm, matrix= x, Number of slices =. AsubsetofhealthycontrolsfromCorticalInhibitionandAttentional CIAM T(Allegra)Siemens. TR/TE,/.ms;flipangle,degrees,FOV,mm 0mm mm;andvoxelsize,.mm.0mm.0mm. Modulation:astudyofpsychosis(CIAM)UCT. ATweighted,Dmagnetizationpreparedrapidgradientechosequence(MPRAGE)(TR/TE/TI/FA=0ms/.ms/00 CLiNG AsampleofhealthycontrolsfromClinicalNeuroscienceGöttingen T(TrioTim)Siemens. ms/ ;imagematrix=x;durationminandsec)wasacquiredgeneratingsagittalsliceswithavoxelsizeof mm. a)mpragescan:scanplane=sagittal,tr/te/ti=/./00ms,grappaaccelerationfactor=,flipangle=, HealthysubjectsfromFunctionBiomedicalInformaticsResearch a)t(timtrio)siemens&b)t(discovery resolution= x,fov=0mm,voxelsize=0.x0.x.mm,andnex=. FBIRN. Network(FBIRN) MR0)GE b)irspgrscan:scanplane=sagittal,tr/te/ti=././ms,assetaccelerationfactor=,aflipangle=, resolution= x,fov=0mm,voxelsize=0.x0.x.mm,andnex= ATweighted,magnetizationpreparedrapidgradientechosequence(MPRAGE)(TR/TE/TI/FA=00ms/.0ms/00ms/ ; HMS HealthysubjectsfromtheHomburgMultidiagnosisStudy.T(Sonata)Siemens. imagematrix=x)wasacquiredgeneratingconsecutivesagittalsliceswithavoxelsizeofmm.~min HUBIN AsampleofhealthysubjectsfromHumanBrainInformatics.T(Signa)GE.0 Tweightedimages,usingathreedimensionalspoiledgradientrecalled(SPGR)pulsesequence,wereacquiredwiththe followingparameters;.mmcoronalslices,nogap, flipangle,repetitiontime(tr)=ms,echotime(te)=.0ms, numberofexcitations(nex)=,fieldofview(fov)=cm,acquisitionmatrix=. IMAGEN TheImaginggeneticsconsortium,anEuropeaninternational populationbasedsample(schumannetal.,) T(Achieva)Philips;TBrucker;T(TrioTim) Siemens;T(Verio)Siemens;T(SignaExcite) Brucker/GE&T(SignaHDx)GE. MagneticresonanceimagingdatawereacquiredatEuropeancenters,usingastandardisedTesla,Tweightedgradient echoprotocol(voxelsize=.mmisotropic)basedonthatfromtheadniinitiative ( IMpACT LBC MAS MCIC MethCT TheInternationalMulticentrepersistentADHDGenetics.T(Avanto)Siemens. Allscanshadavoxelsizeof mm,trms,ti=00ms,te.ms,sagittalslices,fieldofviewmm. CollaboraTion:asubsetDutchhealthycontrols Lothianbirthcohortfrom:Scotishsampleofhealthyolder DIRPrepTweightedwholebrainFSPGRvolumeswereacquiredinthecoronalplaneusingaGESignaHorizonHDxt.T subjects(age~0)bornon,aspartofastudyonbrainagingand.t(signahorizonhdx)ge. clinicalmriscannerwithmanufacturersuppliedeightchannelphasedarrayheadcoil;fov=xmm,matrix=x cognition(wardlawetal.,),x.mmthickslices,xx.mmvoxels,tr=ms,te=msandti=00ms. DTweightedstructural(TwTFE turbofieldecho)mri,acquiredcoronallywithrepetitiontimetr=.ms,echotime Sydney'sMemoryandAgingStudy:anepidemiologicalsampleof T(AchievaQuasarDualscanner)Phillips. TE=.ms,flipangle=,matrixsize=,fieldofviewFOV= 0mm,andslicethickness=mmwith europeansubjectshttp:// nogapbetween;yielding mmisotropicvoxels MINDClinicalImagingConsortiumformedbytheMentalIllnessand TR=msforT,TR=msfor.T;TE=.msforT,TE=.msfor.T;FA=forT,FA=for.T;TI=.TSiemens,T(Trio)Siemens&T(Signa) NeuroscienceDiscovery(MIND)InstitutenowtheMindResearch.0 00forT;Bandwidth=forT,Bandwidth=0for.T;0. 0.mmvoxelsize;slicethickness.mm;FOV GE Network(MRN;http//ww.mrn.org) cmmatrix Healthycontrolsfromstudiesonmethamphetamineuse;Universityof Tweighted,DMEMPRAGEsequence:TR=ms;gradedTE=./././.m;flipangle= ;FOV=mm;slice T(MagnetomAllegra)Siemens. CapeTown thickness=mm MüNC TheMünsterNeuroimagingCohort T(GyroscanIntera),Philips. Tweightedimageswereacquiredusingafastgradientechosequence(turbofieldecho),repetitiontime.milliseconds, echotime.milliseconds,flipangle,acquiredoverafieldofviewof(feethead[fh])(anteriorposterior[ap]) (rightleft)andreconstructedtocubicvoxelsof.mm.mm.mm[rl])mm NCNG NESDA NeuroIMAGE TheNorwegianCognitiveNeuroGeneticssample:apopulationbased.T(Sonata)Siemens&.T(Avanto). sampleofeuropeansubjects(espesethetal.,) Siemens AsubsetofhealthycontrolsfromtheNetherlandsStudyofDepression T(Achieva;Intera)Phillips.0 andanxiety. AsampleofeuropeanhealthycontrolsandhealthysiblingsofADHD.T(Sonata),Siemensand.T(Avanto),. patients Siemens ASiemensSonata.Teslascanner(Siemens,Erlangen,Germany)withaconventionalheadcoilwasused.TwoDMPRAGE Tweightedsequences(duration:mins)wererunforallparticipants.Eachvolumeconsistedofsagittalslices (.xxmm),withaninplanevoxelsizeofmm(tr=ms;te=.ms;ti=00ms;flipangle= ;and matrix).#:asiemensavantoscannerwasusedtoacquiretwodmpragetweightedsequences(tr/te/ti/fa=00 ms/.ms/00ms/ ;matrix= ;durationminandspervolume).eachvolumeconsistedofsagittalslices (...mm) ImagingdatawereacquiredattheLeidenUniversityMedicalCenter,AmsterdamMedicalCenter,andUniversityMedical CenterGroningen,equippedwithaSENSE(LeidenUniversityMedicalCenterandUniversityMedicalCenterGroningen)or SENSE(AmsterdamMedicalCenter)channelheadcoil.Foreachsubject,anatomicalimageswereobtainedusingasagittal DlgradientechoTweightedsequence(TR=ms,TE=.ms;matrix=x;voxelsize=xxmm;0slices; duration=.minutes)..tmriscannerswereemployed(siemenssonataandsiemensavanto;siemens,erlangen,germany),usingidentical headcoils(channelphasearrayheadcoil).tweightedwholebrainscan(mprage,slices,acquisitionmatrix x,voxelsize:.0x.0x.0mm;te/tr=./ms,ti=00ms,fa= ;GRAPPAacceleration) ()SequencenameTTFE.Inplaneresolution mm. matrix.slicethickness.mmwithoutgap.numberof slices:.orientation:cortr/te:./.msflipangle:.scanduration:sec.()acquisitionparametersfort OATS OneindividualperfamilyofTheOlderAustralianTwinsStudy.T(Gyroscan)Philips;T(AchievaQuasar Dual)Philips;.T(MagnetomAvanto) Siemens;.T(Sonata)Siemens. weightedstructuralmriscanswere:tr=.ms,te=.ms,flipangle=,matrixsize=x,fov=xx0,and slicethickness=mmwithnogapbetween;yieldingxxmmisotropicvoxels()inplaneresolution= mm,slice thickness=.mm,slicenumber=,tr(repetitiontime)=ms,te(echotime)=.ms,ti(inversiontime)=0ms, flipangle=andnex(numberofexcitations)=.()inplaneresolution= mm,slicethickness=.mm,slicenumber=, TR(Repetitiontime)=ms,TE(Echotime)=.ms,TI(Inversiontime)=0ms,flipangle=andNEX(Numberof Excitations)=. OCDAMC ControlsubjectsfromstudiesonOCD(pedriatric) T(Intera)Philips. T(PhilipsInteraMR)matrixx,slices,voxelsizexx.mm OCDBarcelona ControlsubjectsfromstudiesonOCD.T(SignaExcite)GE. matrixx,slices,voxelsize.x.x.mm OCDFukuoka ControlsubjectsfromstudiesonOCD T(AchievaTX)Philips. T(PhilipsAchievaTX)matrix0x0,TR.ms,TE.ms,TI(inversiontime)0ms,Flipangledegree,FOV0x0,NSA,Sliceticknessmm,numberofslice0,voxelsize.x...mm,scantimes OCDIndia.T Healthycontrols,examinedusingastructuredinterviewtoruleouta psychiatricdiagnosisorneurologicaldisease.t(vison)siemens..t(siemensvision):matrixx,slices,0.x0.xmm OCDIndiaT Healthycontrols,examinedusingastructuredinterviewtoruleouta psychiatricdiagnosisorneurologicaldisease T(Skyra)Siemens. T(SiemensSkyra):matrixX,slices,voxelsize.0X.0X.0mm; OCDKunming.T ControlsubjectsfromstudiesonOCD.T(SignaExcite)GE..T(SignaExcite)GE:matrixx,slices,voxelsize0.x0.x0.mm OCDKunmingT ControlsubjectsfromstudiesonOCD T(Achieva)Philips. T(Achieva)Philips:matrixx,slices,FOV=,voxelsize.x.x0.mm OCDKyoto.T ControlsubjectsfromstudiesonOCD.T(GyroscanIntera)Philips. OCDKyotoT ControlsubjectsfromstudiesonOCD T(Achieva.0TX)Philips. OCDLondon ControlsubjectsfromstudiesonOCD.T(Signa)GEand.T(SignaHDx)GE. OCDShanghai ControlsubjectsfromstudiesonOCD T(Verio)Siemens. OCDSNUA ControlsubjectsfromstudiesonOCD.T(Signa)GE. ThreedimensionalvolumetricacquisitionofaTweightedgradientechosequenceproducedagaplessseriesofcontiguous, thinsagittalsectionswiththefollowingparameters:flipangle, ;acquisitionmatrix, ;fieldofview,cm;section thickness,.mm;voxelsize,0.mm 0.mm.mm;TR,.ms;TE,.ms. ThescanningparametersoftheTweightedthreedimensionalmagnetizationpreparedrapidgradientecho(DMPRAGE) sequenceswereasfollows:flipangle,degrees;acquisitionmatrix,xx0;fieldofview,.cm;sectionthickness,.0mm;voxelsize,.0mmx.0mmx.0mm;tr,.ms;andte,.ms. Sequence:DSPGR,TR:.ms,TE:.ms,FA:º,Orientation:Axial,Matrixsize:xx,Voxelsize:0.x0.x.0;Sequence:DSPGR,TR:.ms,TE:.0ms,FA:º,Orientation:Axial,Matrixsize:xx,Voxelsize:.0x.0x. T(Siemensverio)matrixx,slices,slicetickness.0mm,voxelsizexxmm,TRms,TE.ms,FOV x0,flipangledegree MPRAGEsequencewereacquiredincontiguousaxialslices:TR/TE=0/.ms,fieldofview=cm,flipangle=, matrixx,voxelsize0.x0.x0.0mm. Contiguous.mmsagittalimageswereobtainedwithathreedimensionalTweightedspoiledgradientechosequence OCDSNUB ControlsubjectsfromstudiesonOCD.T(Avanto)Siemens. (echotime=.ms;repetitiontime=.ms;flipangle= ;fieldofview= cm;matrixx;voxelsize 0.x0.x.0mm). HighresolutionTweighted,threedimensionalMPRAGE(TR=0ms;TE=.ms;FOV=0mm;FA= ;matrixx; OCDSNUC ControlsubjectsfromstudiesonOCD T(MagnetomTrio)SIemens. voxelsize.000x0.x0.mm). TweightedMPRAGEsagittalDvolume(TR=ms;TE=.ms;TI=00ms;slices;FOV=x0mm;voxel OCDSU ControlsubjectsfromstudiesonOCD T(MagnetomAllegra)Siemens. size=.x.0x.0mm;slicethickness=mm,flipangle=degrees OCDVUmcAmsterdam.T ControlsubjectsfromstudiesonOCD.T(Sonata)Siemens..T(SiemensSonata)matrixx,slices,voxelsizexx.mm OCDVUmcAmsterdamT ControlsubjectsfromstudiesonOCD T(SignaHDxt)GE. T(SignaHDxt)matrixx,slices,voxelsizex0.x0.mm OCDZurich Healthycontrolsubjects(adolescentsandadults) T(Achieva)Philips. T(PhilipsAchieva)matrix0x0,slices,voxelsizeisotropicxxmm,TR.ms,TE.ms,Flipangledegree TweightedIRFSPGRsagittalDvolume(TR=.ms;TE=.ms;TI=0ms;slices,matrixsize=x, Osaka.T ControlsubjectsfromtheJapaneseOsakacasecontrolstudiesof schizophrenia.t(signa)ge&t(signahdxt)ge. FOV=.0x.0cm,voxelsize=0.x0.x.mm,slicethickness=.mm,flipangle= )TweightedIRFSPGR sagittaldvolume(tr=.ms;te=.ms;ti=0ms;slices,matrixsize=xx,fov=.0x.0cm,voxel size=0.x0.x.0mm,slicethickness=.0mm,flipangle= ) TweightedIRFSPGRsagittalDvolume(TR=.ms;TE=.ms;TI=0ms;slices,matrixsize=x, OsakaT ControlsubjectsfromtheJapaneseOsakacasecontrolstudiesof schizophrenia.t(signa)ge&t(signahdxt)ge. FOV=.0x.0cm,voxelsize=0.x0.x.mm,slicethickness=.mm,flipangle= )TweightedIRFSPGR sagittaldvolume(tr=.ms;te=.ms;ti=0ms;slices,matrixsize=xx,fov=.0x.0cm,voxel size=0.x0.x.0mm,slicethickness=.0mm,flipangle= ) PAFIPIDIVAL Healthycontrolsfromstudiesonschizofrenia.T(Signa)GE.0 Tweightedimages,usingaspoiledgrass(SPGR)sequence,wereacquiredinthecoronalplanewiththefollowing parameters:te=ms,tr=ms,nex=,fa=o,fov=x.cm,slicethickness=.mmandamatrixofx PAFIPIDIVAL Healthycontrolsfromstudiesonschizofrenia T(Achieva)Phillips. SagittalT,TR=00ms;TE=.ms;FA=o;Voxelsize=xxmm;Slicethickness=mm;Matrixsize=x PAFIPIDIVAL Healthycontrolsfromstudiesonschizofrenia.T(Signa)GE.0 QTIM AnaselectsubsetoftwinsingletonsofeuropeandescentfromThe QueenslandTwinImagingstudy. T(Bruker)Medspec. SHIP PopulationbasedsamplefromTheStudyofhealthinPomerania (northeasterngermany).t(avanto)siemens. SHIPT PopulationbasedsamplefromTheStudyofhealthinPomerania (northeasterngermany).t(avanto)siemens. STROKEMRI Healthycontrolsfromanongoingstrokestudy,Oslo T(HDxT)GE. TCD NUIG HealthysubjectsfromTCD(Dublin)andNUIG(Galway) TCD:T(Intera)Philips;NUIG:.T TCD:.NUIG:. (Magnetom),Siemens TOP ControlsubjectsfromTematiskOmrådePsykoser(Thematically OrganizedPsychosisResearch)..T(Sonata)Siemens HealthycontrolsfromtheBipolarGeneticsdataset.ThisNIMHfunded 0 UCLA NLBP studyiscarriedoutattheuniversitymedicalcenterutrecht,the Netherlands,inacollaborationwiththeUniversityofCaliforniaLos. T(Achieva)Philips Angeles UMCU Healthycontrolsfromtwoindependentschizophreniacohorts recruitedattheuniversitymedicalcentreutrecht,thenetherlands..t(achieva)philips Tweightedimages,usingaspoiledgrass(SPGR)sequence,wereacquiredinthecoronalplanewiththefollowing parameters:te=ms,tr=ms,nex=,fa=o,fov=x.cm,slicethickness=.mmandamatrixofx ScanswerecollectedonaTeslaBrukerMedspecscanner(Bruker,Germany).Tweightedstructuralscanswereacquired withacquisitionparameters:tr=0ms,te=.ms,ti=00ms,flipangle=,or0(coronalorsagittal)slices, FOV=0mm,acquisitionvoxelsize.x0.x0.mm. DTweightedMRIsequencewiththefollowingparameters:MPRAGE/axialplane,TR=00ms,TE=.msandFlip angle= andanoriginalresolutionof.0x.0x.0mm DTweightedMRIsequencewiththefollowingparameters:MPRAGE/axialplane,TR=00ms,TE=.msandFlip angle= andanoriginalresolutionof.0x.0x.0mm SagittalTweightedFSPGRsequence(TE:.,TR:.ms,flipangle:degrees,voxelsixe=xx.millimeter,number ofslices:) TCD:TweightedTFEgradientecho(TE(ms).;TR(ms).;Flipangle( );FOV;Matrixx;No.slices; slicethickness(mm)0.;voxelsize(mm)0.x0.x0.);nuig:.t:tweightedmprage(te(ms).;tr(ms); Flipangle( );FOV;Matrixx(kspaceinterpolationfromx);No.slices;slicethickness(mm)0.; Voxelsize(mm)0.x0.x0.) TwosagittalTweightedmagnetizationpreparedrapidgradientecho(MPRAGE)volumeswereacquiredwiththeSiemens tfld_nspulsesequence(te=.ms,tr=ms,ti=00ms,flipangle= ;FOV=cm,voxelsize=.x0.x mm,numberofpartitions=) ThreedimensionalTweightedimageswereacquiredonaTeslaPhilipsAchievascanner(PhilipsHealthcare,Best,the Netherlands),equippedwithanchannelSENSEheadcoil.Fastfieldechoscanswith0contiguoussagittalslices(TE=. ms,tr=ms,flipangle=,fov=0mm,0.x0.x0.0mm³voxels)wereobtained. AThreeDimensionalFastFieldEcho(DFFE)ona.TPhilipsAchievascanner:TE=.ms,TR=ms,flipangle=, FOV=xmm)withcontiguouscoronal.mmslices Würzburg Tübingen DatasetofhealthycontrolsfromastudyonADHD.T(Avanto)Siemens. AhighresolutionTweightedmagnetizationpreparedrapidgradientechoimaging(MPRAGE)DMRIsequencewas obtainedfromeachparticipant(tr:0ms,te:.ms, flipangle,fov:mm,matrix:,voxelsize: mm

4 SupplementalInformationS.Listofdatasets(arrangedalphabetically)onwhichhandednessanalyseswereperformed, correspondingsamplesizesandassessmentmethods. Dataset Left Right handed handed Assessment BIG.T 0 Selfreport BIGT 0 Selfreport BIL&GIN Selfreport CLiNG SelfreportconfirmedbyEdinburghHandednessInventory FBIRN Selfreport HMS SelfreportconfirmedbyEdinburghHandednessInventory HUBIN 0 Selfreport IMAGEN SelfreportconfirmedbyPurduePegboardtest IMpACT Selfreport LBC Writinghand MCIC AnnettScaleofHandPreference MüNC EdinburghHandednessInventory:Athresholdof(outof)itemswasusedto categorizeasleftorrighthanded. NCNG Selfreport NESDA Selfreport NeuroIMAGE Selfreport OCDVUmcAmsterdam.T Selfreport OCDVUmcAmsterdamT Selfreport Osaka.T SelfreportconfirmedbyEdinburghHandednessInventory OsakaT SelfreportconfirmedbyEdinburghHandednessInventory SHIP Selfreport SHIPTrend Selfreport STROKEMRI Selfreport TOP Selfreport UCLA NLBP Selfreport UMCU Selfreport

5 SupplementalInformationS:Leftrightflipchecks Ofspecialimportancewastoassurethecorrectcorrespondencebetweentheleft/rightorientationoftheprocessed imagedataandtheoriginalsubjectspace.incontrasttotheotheraxes(anteroposteriororsuperiorinferior),the correctorientationontheleftrightaxisisnotdirectlyidentifiablefromvisualfeatures,makingitdifficulttoreadily detectanyerroneousimageflipsduringprocessing.suchproblemsaremuchmoreunlikelysincetheadoptionofthe niftiimagingstandard( DICOMformatted)dataisprocessedwithincorrectassumptions(SPMdocumentation,p.; BecausetheENIGMAprotocolstartsaftertheraw(oftenDICOMformatted)datahasbeenconvertedintoanimaging standard(orconvertedbyfreesurferitself),thismeantthatconversionfromthedicomformatwasthemostlikely stepwhereanyerrorcouldhavetakenplace.thiswasassessedusingseveralstrategies,dependingontheavailable informationateachsite.thebil&gin,fbirn,mas,nesdaandoatssampleshadmadeuseofparamagneticfiducial markersonasubsetoftheirsubjects,thuseliminatingorientationambiguity.inqtimandship,subjectswithaknown unilateralbrainabnormalitywereusedtocheckthecorrectorientationoftheimageafterconversion.inbig,cling, HMSandOCDSU,afewexamplesweremanuallycheckedformismatchesbetweentheDICOMandniftiheader information,i.e.acorrectflipfrom'radiological'to'neurological'orientation.finally,wecheckedtheconsistency betweenseveral,commonlyused,dicomtonifticonversiontoolsanddicomimagesgeneratedfromdifferent manufacturers/models(usingexamplesdownloadedfromthemanufacturer'swebsites).theconvertorsusedinthis stepwere:"mri_convert"( MRIConvert"( ( Giventhatthesechecksyieldednoproblems,andthatthedatasetswherenoerrorwasdetectedcomprised0%ofthe totalmetaanalysissample,wewereconfidentthatsuchorientationerrorsmusthavebeenveryunlikely.

6 Supplementary Information S. Plots of the relationship between and subcortical AIs in the BIG T sample. Regression analyses of linear and quadratic relationships revealed only linear effects of with AIs of the nucleus accumbens, caudate nucleus and putamen (as indicated by the dashed lines).

7 N. accumbens AI against Accumbens AI Amygdala AI Amygdala AI against Thalamus AI against Thalamus AI Caudate N. AI against Caudate AI

8 Putamen AI against Putamen AI Globus Pallidus AI against Globus pallidus AI Hippocampus AI against Hippocampus AI

9 Supplementary Information S. Boxplots of AI distributions for each dataset and structure. For each structure, the datasets are ordered top-to-bottom by their median AIs. The identities of the datasets are given by the numbers in the lefthand columns, with reference to Table. The horizontal length of each box represents the nd to rd quartile of the AI distribution (i.e. containing half of subjects in each dataset) and split at the median AI. The vertical width of each dataset's box is proportional to the square root of its sample size. The whiskers show the minimum and maximum values (curtailed in cases where the outer box boundary was reached). The vertical dotted lines indicate the points of perfect symmetry, AI=0.

10 N. accumbens Amygdala Caudate N Globus pallidus Hippocampus Putamen Thalamus

11 Supporting Information S. Meta-analyzed results from testing population-level lateralization (mean AI's 0) separately by sex. A positive Z-score indicates leftward asymmetry in volume (L>R), while a negative Z-score reflects a rightward asymmetry (R>L). Females N z-score Males N z-score Nucleus accumbens -.0 Nucleus accumbens Amygdala 0 -. Amygdala -. Caudate nucleus 0 -. Caudate nucleus -. Globus pallidus. Globus pallidus 0. Hippocampus -. Hippocampus 0 -. Putamen. Putamen 0. Thalamus 0. Thalamus.

12 Phenotype Phenotype Phenotype correlation Phenotype correlation P Genetic correlation Genetic correlation P AI_amygdala AI_accumbens AI_amygdala AI_caudate AI_amygdala AI_hippocampus AI_amygdala AI_pallidum AI_amygdala AI_putamen AI_amygdala AI_thalamus AI_caudate AI_accumbens AI_caudate AI_hippocampus AI_caudate AI_pallidum AI_caudate AI_putamen 0..E AI_caudate AI_thalamus AI_hippocampus AI_accumbens AI_hippocampus AI_pallidum AI_hippocampus AI_putamen AI_hippocampus AI_thalamus 0..E AI_pallidum AI_accumbens AI_pallidum AI_putamen AI_pallidum AI_thalamus -0..E AI_putamen AI_accumbens AI_putamen AI_thalamus -0..E AI_thalamus AI_accumbens Supplementary Information S. Phenotypic and genetic correlations among AIs in the GOBS dataset.

Supplementary Table S3: Instrument for diagnosing Major Depressive Disorder and exclusion criteria by site.

Supplementary Table S3: Instrument for diagnosing Major Depressive Disorder and exclusion criteria by site. Supplementary Tables Supplementary Table S1: ENIGMA - Major Depressive Disorder Working Group Demographics. Age (in years), sex, and patients-control breakdown for participating sites Supplementary Table