hispanic community health study / study of latinos (hchs -sol) · national institute of...

HispanicCommunityHealthStudy/StudyofLatinos(HCHS- SOL)

NationalHeart,Lung,andBloodInstituteNationalInstituteofDiabetesandDigestiveandKidneyDiseases

NationalInstituteofNeurologicalDisordersandStrokeNationalInstituteofDeafnessandOtherCommunicationDisorders

NationalInstituteofDentalandCraniofacialResearchNationalInstituteforMinorityHealthandHealthDisparities

OfficeofDietarySupplements

ChallengestoHealthDisparitiesResearch

• Barriers– LegalStatus– PastTraumas–Discrimination–Marginalization–DistrustofGovernment– CulturalorLinguisticDifferences

2(USC, Center for Health Journalism)

Hispanic/LatinoDefined

Jaimes, Londono, Halpern, JAMA Dermatol, 2013

A- Latino refers to persons whose origin or ancestries are from countries of Latin America.

B-The US Office of Management and Budget uses the terms Hispanic and Latino interchangeably to refer to persons who indicated that their origin is Mexican, Puerto Rican, Cuban, Central and South American, or other Spanishculture or Spanish-speaking country or origin, regardless of race.

C-Hispanic include individuals whose origin or ancestry comes from Hispania, or D-Spanish-speaking persons of Latin American descent living in the United States.

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GrowthanddiversificationofUSLatinopopulation

USHispanic/Latinos

1980 1990

2000 2010Pew Hispanic Center (www.pewhispanic.org)

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HCHS- SOLcohortoverview• Multicenterprospectivecohortrecruitedin2008-2011

• N=16,415participantsaged18to74yearsold1/3ofparticipantswere18-45yearsatbaseline (undersampled)2/3ofparticipantswere>45yrs atbaseline(oversampled)AreabasedhouseholdsampleinfourUScities

• TOPMed contactPIs:RobertKaplanandKariNorth• GeneticSIGchairs:K.North,E.Boerwinkle,T.Sofer• GeneticAnalysisCenter:BruceWeirandCathyLaurie• OthersitePIs:M.Daviglus (Chicago),N.Schneiderman (Miami),G.Talavera(SanDiego),J.Cai(CC)

• SpirometryreadingcenterPIs:GrahamBarr,PaulEnright,JohnHankinson

RecruitmentN=16,415,ages

18-74

Annualfollow-upinterviewstodetermineoutcomesandchangesinkeyexposures2009-

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

Secondclinicvisit2014-2017

Baselineclinicvisit2008-2011

StudyTimeline

Diseaseandbiometricphenotypes• Prevalent and incident pulmonary diagnoses + exacerbations• Pulmonary Function Testing (basal and post-bronchodilator)• Mortality (total and cause-specific)• Prevalent and incident CVD (MI, stroke, heart failure)•Anthropometry/Weight loss/gain • Lab values: lipids, glucose, OGTT, insulin, inflammation, CBC, Hepatitis A, B C, Total and HDL cholesterol, LFT, renal, etc• Oral/dental health• Pregnancy complications•Hearing • Blood pressure, ECG, echocardiography• Sleep quality and disorders • Cognitive Function• Substance Abuse • Diabetes• Health behaviors (smoking, diet, physical activity, etc)

StudyPopulation

Miami,FL

Chicago,IL

SanDiego,CA

Bronx,NY

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• HispanicCommunityHealthStudy/StudyofLatinos(HCHS/SOL)– Community-basedstudyof16,415menandwomen,18-76yearsofageatbaselineexamination(2008-2011)

– Complexsamplingdesign– Self-identifiedas

• CentralAmerican• Cuban• Dominican• Mexican• PuertoRican• SouthAmerican• Other/Multiple

Pew Hispanic Center (www.pewhispanic.org)

4outof5cohortmemberswerebornoutsideofthe50states

Lengthoftimelivinginthe50statesondateofenrollment

DemographicCharacteristics

All Cuba Domin.Republic

Mexico PuertoRico

Cent.Amer.

So.Amer.

N 16,415 2,201 1,400 6,232 2,590 1,634 1,022

Men,% 40 46 34 37 41 39 40

College,% 15 20 15 12 14 14 22

Income>$50K,% 11 8 7 14 14 7 11

PreferSpanish,% 77 91 80 81 42 89 89

USresidence<10years,% 31 55 27 27 8 38 47

Daviglus ML JAMA 2012

Asthmaprevalence

Mexican PuertoRican

Cuban CentralAmerican

Dominican SouthAmerican

Physician-diagnosedasthma,ever

7.8(6.8–8.9)

30.9(27.8–34)

23.3(21.1–25.7)

12.8(10.7–15)

15.7(13.0–18.7)

10.4(7.9–13.5)

Physician-diagnosedasthma,current

3.4(2.7–4.1)

15.3(13.2–17)

8.6(7.1–10.4)

4.5(3.4–6.0)

6.7(5.3–8.5)

4.3(2.9–6.2)

AsthmaprevalenceishighestinLatinoswhocametothe50statesduringearlychildhood

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Estimated prevalence of asthma by age immigrated to US

Age immigrated to US

Prev

alenc

e of

ever

asth

ma

diagn

osed

by M

D

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0

10

20

30

40

50

60%

1 5 10 15 20 25 30 35 40 45 50 55 60 65 70US

born

Note: Prevalence estimates and 95% confidence intervals are from a survey data logistic regression model with effects for age(continuous), sex, Hispanic background, and age at immigration (grouped into 65 categories)

GrahamBarrAmJRespir Crit CareMed 2015

+

ElinaJerschow AmericanJournalofPreventiveMedicine2017

SOLGeneticProjects

• Omics inLatinos(OLa)GWAS

• PAGEconsortium– Metabochip– MEGAchip

• Wholegenomesequencing

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SOLGeneticProjects




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OLa GWASProjectSNPMicroarrayData

12,803studyparticipantsprovidedconsentforgeneticstudies

Illumina Omni2.5M+~150kcustomcontent‘SoL_HCHS_Custom_15041502_B’

Arraydesign– Papanicolaou(NHLBI),RotterandTaylor(LABiomed)

GenotypingperformedbyIllumina &QCbyLABiomed

QAbySOLGeneticAnalysisCenter(Univ.Washington)

Imputationto1000Gphase3

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AnkleBrachialIndex Dental

Anthropometrics Diabetes

Anxiety/Depression Electrocardiography

BloodCellCount PulmonaryDisease

BloodPressure Sleep

ChronicKidneyDisease mtDNA/YChr

Lipids Reproductivetraits

Smoking

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SOLGeneticAnalysisWorkingGroups

www.olgastudy.org

20ScrolldownforallworkinggroupsandtheirmembersDirectoryhascontactinformation

1.EstimaterelatednessusingKING-robust,whichisrobusttodiscretepopulationstructurebutnottoadmixtureordeparturesfromHWEwithinsub-populations.

2.Partitionthesampleintoamutuallyunrelatedsetandtheremaining(relativesoftheunrelatedsetandpossiblyeachother)

3.Performstandardprincipalcomponentsanalysis(PCA)onthesetofunrelatedindividualsandprojectontorelatedindividuals

4.Re-estimaterelatednessusing‘PC-Relate’,whichprovidesunbiasedkinshipcoefficientsinthepresenceofpopulationstructure,admixtureandHWEdepartures,usingindividual-specificallelefrequenciesestimatedfromsampleeigenvectors.

5.Repeatsteps2-5togetfinalsetsofeigenvectorsandkinshipcoefficients

De-convolutionofancestryandrelatednessinadmixedpopulationsMattConomos andTimThornton(UniversityofWashington)

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GeneticAnalysisIssues1. Tieredconsentallowsvariablelevelsofdatasharing.Reconsentingat

eachinpersonvisitmaynecessitatewithdrawalofsubjects

1. Samplesurveydesign,2-stageprobabilitysamplinga. Primarysamplingunit=UScensusblockgroupb. Secondarysamplingunit=householdc. Householdbasedsampling(average1.8enrolledperHH)

2. Relatedness,populationstructureandadmixturea. ~85%ofsubjectsaremutuallyunrelatedb. ~15%areeachrelatedtosomeoneintheunrelatedsetc. SOLparticipantsareverydiverseethnicallyandgenetically

i. Caribbeangroups:Cuban,Dominican,PuertoRicanii. Mainlandgroups:Mexico,CentralAmerica,SouthAmerica

d. Novelmethodusedtode-convoluteancestryandrelatedness(Conomos &Thornton)

MixedmodelandGEEapproacheshavebeendevelopedtohandletheseissuesinassociationtests(GWAS).BothcontrolTypeIerrorwell,butmixedmodelhasmorepower.(Mixedmodel– Conomos +Thornton;GEE- Lin+Tao)

Populationstructure

Principalcomponentsanalysis(PCA)

Conomos 2016.

PCAplots(EV1-3)

Proportionofancestralbackgrounds

Conomos etal.2016.

ContinentalancestryproportionsestimatedusingADMIXTUREsoftwareAutosomal

Xchromosome

SeparatePCAforeachofthe3ancestries

HCHS-SOLgroups

Referencepopulations

SharonBrowningG32016

SeparateclusteringofAfricancomponentofHondurans/Guatemalans

• Garífuna population.

• MayhaveancestryfromspecificpartsofAfrica.

• Ordriftduetosmallpopulationsize.

HCHS-SOLgroups


Africa


ThreedistinctAmerindianclusters

• Mexico,CentralAmerica,SouthAmerica.

HCHS-SOLgroups


Americas


SeparateclusteringofEuropeancomponentofPuertoRicans

• MayincludeancestryfromNorthAfricanorMiddleEast.

• Ordriftduetosmallpopulationsize.

HCHS-SOLgroups


Europe


Eachofthefirst5Eigenvectorsdifferentiatesamongself-identifiedgroups

• Usethese5eigenvectorstoadjustforancestryinassociationtestsandtodefinegeneticanalysisgroupsforstratifiedanalysis• Comparedwithself-identifiedbackground(personalorfamilyplaceoforigin),thegroupsaremorehomogeneousgeneticallyandincludeindividualswithmissingor“other”self-identification 31

SOLGeneticProjects




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KariNorthUNC-CH

CALiCOConsortium

PopulationArchitectureusingGenomicsandEpidemiology(PAGE)Study

RuthLoosMountSinaiSchoolofMedicine

MSSMBiobank

TaraMatiseRutgersUniversity

CoordinatingCenterCharlesKooperbergFHCRC

Women’sHealthInitiative

ChrisHaimanUSC

MultiethnicCohortStudy

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ThePAGEStudyPopulationArchitectureusingGenomicsandEpidemiologyIINetwork

• Goal:Investigateancestrallydiversepopulationstogainabetterunderstandingofhowgeneticfactorsinfluencesusceptibilitytodisease.

• FocusonUSminoritypopulations.

17,328

4,696

22,250

653

3,944

1,056

African-American

Asian

Hispanic/Latino

NativeAmerican

NativeHawaiian

Others

ILLUMINA ARRAY SEMINAR, SEPTEMBER 2016

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Common Low Frequency Rare

AAC

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0.04,

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0.03,

0.04

0.02,

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0.01,

0.02

0.005

, 0.01

Variant Frequency

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Omni1MOmniExpressAxiom.AFRMEGA

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Variant FrequencyIm

puta

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, Mea

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AMR

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Variant Frequency

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Omni1MOmniExpressAxiom.LATMEGA

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SAS

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Omni1MOmniExpressAxiom.EASMEGA

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EAS

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0.04,

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0.02

0.005

, 0.01

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ComparisonofMEGAImputationAccuracytoOtherCommercialChips(SupplementaryFigure)

SOLGeneticProjects




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HCHS/SOLsampleselectionforwholegenomesequencingN=1917asthmacases(everdiagnosedbyaphysician)N=4503controls(neverdiagnosedbyaphysician)

NHGRI/PAGE ~270samplesselectedforhighAmerindianancestryPrimarilyCentralandSouthAmerican(onlyonePuertoRican)WashingtonU.sequencingcenter

NHGRI/CCDG ~4000samplesselectedatrandom Baylorsequencingcenter

TOPMed Totalapprovedallocationof2150 Baylorsequencingcenter1. Allever-asthmacasesnotpreviouslyselectedbyPAGEorCCDG,N=1277.(Bringing

totalofever-asthmacasesto1917acrossallthreesampleselections)

2. SixsamplespreviouslyselectedbyPAGE,whichwillserveascross-sequencingcentercontrols(onepergeneticanalysisgroupe.g.Cuban,Mexican,Dominican,etc),N=6

3. RemainingPuertoRicansnotincludedinPAGEorCCDGselections,N=867.

WethanktheparticipantsandstaffoftheHispanicCommunityHealthStudy/StudyofLatinos(HCHS/SOL)fortheircontributionstothisstudy.ThebaselineexaminationofHCHS/SOLwascarriedoutasacollaborativestudysupportedbycontractsfromtheNHLBItotheUniversityofNorthCarolina(N01-HC65233),UniversityofMiami(N01-HC65234),AlbertEinsteinCollegeofMedicine(N01-HC65235),NorthwesternUniversity(N01-HC65236),andSanDiegoStateUniversity(N01-HC65237).Thefollowinginstitutes,centers,andofficescontributedtothefirstphaseofHCHS/SOLthroughatransferoffundstotheNHLBI:NationalInstituteonMinorityHealthandHealthDisparities,NationalInstituteonDeafnessandOtherCommunicationDisorders,NationalInstituteofDentalandCraniofacialResearch(NIDCR),NationalInstituteofDiabetesandDigestiveandKidneyDiseases(NIDDK),NationalInstituteofNeurologicalDisordersandStroke,andNIHOfficeof DietarySupplements.TheGeneticAnalysisCenterattheUniversityofWashingtonwassupportedbyNHLBI andNIDCRcontracts(HHSN268201300005CAM03and MOD03).Additional analysissupportwasprovidedby1R01DK101855-01and13GRNT16490017.GenotypingeffortsweresupportedbytheNIHDepartmentofHealthandHumanServices(HSN26220/20054C),NationalCenterforAdvancingTranslationalScienceClinicalTranslationalScienceInstitute(UL1TR000124),andNIDDKDiabetesResearchCenter(DK063491).

hispanic community health study / study of latinos (hchs -sol) · national institute of...

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