REVIEW ARTICLE The Use of Racial, Ethnic, and Ancestral Categories in Human Genetics Research

14 Pages·2005·0.13 MB·English

Am.J.Hum.Genet.77:000–000,2005
REVIEW ARTICLE
The Use of Racial, Ethnic, and Ancestral Categories in Human Genetics
Research
Race, Ethnicity, and Genetics Working Group*
NationalHumanGenomeResearchInstitute,Bethesda
The global dispersal of anatomically modern humans over the past 100,000 years has produced patterns of phe-
notypic variation that have exerted—and continue to exert—powerful influences on the lives of individuals and
theexperiencesofgroups.Therecencyofourcommonancestryandcontinuedgeneflowamongpopulationshave
resulted in less genetic differentiation among geographically distributed human populations than is observed in
many other mammalian species. Nevertheless, differences in appearance have contributed to the development of
ideas about “race” and “ethnicity” that often include the belief that significant inherited differences distinguish
humans. The use of racial, ethnic, and ancestral categories in genetics research can imply that group differences
arise directly through differing allele frequencies, with little influence from socially mediated mechanisms. At the
same time, careful investigations of the biological, environmental, social, and psychological attributes associated
withthesecategorieswillbeanessentialcomponentofcross-disciplinaryresearchintotheorigins,prevention,and
treatment of common diseases, including those diseases that differ in prevalence among groups.
Introduction Investigations that fail to recognize and acknowledge
the full range of mechanisms through which designa-
Human genetics research is generating unprecedented tions of race, ethnicity, and ancestrycancorrelatewith
amounts of data about the genetic differences among personal traits and health outcomes threaten to rein-
individualsandgroups.Investigationofthesedifferences forcewidelyheldstereotypes.Yetgeneticsresearchalso
willtransformourunderstandingoftheoriginsandna- hasthepotential,bydelineatingthecomplexoriginsof
ture of human diseases (Collins et al. 2003). traits and the closebiologicalaffinitiesbetweenhuman
Research into human geneticdifferencesalsohasthe groups, to help dispel these stereotypes.
potentialtogenerategreatcontroversy.Inthepast,con- The sequencing of the human genome (International
cepts drawn from geneticshavebeenused—bothbyge- Human Genome Sequencing Consortium 2001; Venter
neticistsand by individuals outside the field—tojustify etal.2001)andtheongoinginternationalefforttocat-
andperpetuateracialandethnicdiscrimination(Kevles alog common haplotypes in several populations (Inter-
1985; Provine 1986). The belief that racial and ethnic national HapMap Consortium 2003) make thisanop-
groupshavesubstantial,well-demarcatedbiologicaldif- portune time to examine the complex relationshipsbe-
ferences and that these differences are important has tween genetics research and the categories ofrace,eth-
contributed to many of the great atrocities of the 20th nicity, and ancestry. Although such a review inevitably
century and continues to shape personal interactions drawsonverydifferentacademicdisciplinesandlitera-
and social institutions(Mosse1985;Shipler1997).Be- tures, a cross-disciplinary conversation is essential for
cause of the history of misuse of genetics ideas,geneti- reconciliation of the promise of genetics research with
cists have a special responsibility to examine carefully thehistoricalandpotentialabusesofideasdrawnfrom
theiruseofracialandethniccategoriesintheirresearch. genetics.Thisreviewsummarizeswhatisknownabout
patterns of human genetic variation; the historical de-
ReceivedOctober20,2004;acceptedforpublicationJuly27,2005; velopment of widely held conceptions about race, eth-
electronicallypublishedAugust29,2005. nicity, and ancestry;andtheinteractionsbetweenthese
Addressforcorrespondenceandreprints:SteveOlson,7609Sebago
conceptions and human genetics research.
Road,Bethesda,MD20817.E-mail:[email protected]
* TheRace,Ethnicity,andGeneticsWorkingGroupoftheNational The Origins, Patterns, and Physical Manifestations
HumanGenomeResearchInstituteincludesKateBerg,VenceBonham,
of Human Genetic Variation
JoyBoyer,LarryBrody,LisaBrooks,FrancisCollins,AlanGuttmacher,
JeanMcEwen,MaxMuenke,SteveOlson,VivianOtaWang,Laura The Origins of Modern Humans
LymanRodriguez,NadarajenVydelingum,andEstherWarshauer-Baker.
Information about the history of our species comes
Thisarticleisinthepublicdomain,andnocopyrightisclaimed.
0002-9297/2005/7704-00XX fromtwomainsources:thepaleoanthropologicalrecord
000
000 Am.J.Hum.Genet.77:000–000,2005
and historical inferences based on current genetic dif- ricafollowedbyasubsequentexpansioninnon-African
ferences observed in humans. Although bothsourcesof populations,andthedatescalculatedfortheexpansions
informationarefragmentary,theyhavebeenconverging generallycoincidewiththearchaeologicalrecord(Jorde
in recent years on the same general story. et al. 1998).
The existing fossil evidence suggests that anatomi- Aspectsoftherelationshipbetweenanatomicallymod-
cally modern humans evolved in Africa, within the last ern and archaic humans remain contentious. Studiesof
∼200,000 years, from a pre-existing population of hu- mtDNA (Ingman et al. 2000), the Y chromosome (Un-
mans (Klein 1999). Although it is not easy to define derhilletal.2000),portionsoftheXchromosome(Kaess-
“anatomically modern” in a way that encompasses all mannetal.1999),andmany(thoughnotall)autosomal
livinghumansandexcludesallarchaichumans(Lieber- regions(HarpendingandRogers2000)supportthe“Out
man et al. 2002), the generally agreed-upon physical of Africa”account of humanhistory,inwhichanatom-
characteristics of anatomical modernity include a high ically modern humans appeared first in eastern Africa
rounded skull, facial retraction, and a lightandgracile, and then migrated throughout Africa and into the rest
as opposed to heavy and robust, skeleton (Lahr 1996). of the world, with little or no interbreeding between
Early fossils with these characteristics have been found modern humansandthearchaicpopulationstheygrad-
in eastern Africa and have been dated to ∼160,000– uallyreplaced(Tishkoffetal.2000;Stringer2002).How-
200,000yearsago(Whiteetal.2003;McDougalletal. ever, several groups of researchers cite fossil and genetic
2005). At that time, the population of anatomically evidencetoargueforamorecomplexaccount.Theycon-
modern humans appears to have been small and local- tendthathumansbearingmoderntraitsemergedseveral
ized(Harpendingetal.1998).Muchlargerpopulations times from Africa, over an extended period,andmixed
of archaic humans lived elsewhere in the Old World, witharchaichumansinvariouspartsoftheworld(Hawks
including the Neandertalsin Europeandanearlierspe- etal.2000;Eswaran2002;Templeton2002;Zie˛tkiewicz
cies of humans, Homo erectus, in Asia (Swisher et al. etal.2003).Asaresult,theysay,autosomalDNAfrom
1994). archaichumanpopulationslivingoutsideAfricapersists
Fossils of the earliest anatomically modern humans inmodernpopulations,andmodernpopulationsinvari-
found outside Africa are from two sites in the Middle ous parts of the world still bear some physical resem-
East and date to a period of relative global warmth, blance to the archaic populations that inhabited those
∼100,000yearsago,thoughthisregionwasreinhabited regions (Wolpoff et al. 2001).
by Neandertals in later millennia as the climate in the However, distinguishingpossiblecontributionstothe
northernhemisphereagaincooled(LahrandFoley1998). genepoolofmodernhumansfromarchaichumansout-
Groupsofanatomicallymodernhumansappeartohave side Africa is difficult, especially since many autosomal
moved outside Africa permanently sometime 160,000 locicoalesceattimesprecedingtheseparationofarchaic
years ago. One of the earliest modern skeletons found human populations (Pa¨a¨bo 2003). In addition, studies
outside Africa is from Australia andhasbeendatedto ofmtDNAfromarchaicandmodernhumansandextant
∼42,000yearsago(Bowleretal.2003),althoughstudies Y chromosomessuggestthatanysurvivinggeneticcon-
ofenvironmentalchangesinAustraliaargueforthepres- tributions of archaic humans outside Africa must be
enceofmodernhumansinAustralia155,000yearsago small, if they exist at all (Krings et al. 1997; Nordborg
(Miller et al. 1999). To date, the earliest anatomically 1998; Takahata et al. 2001; Serre et al. 2004). The ob-
modern skeleton discovered from Europe comes from servation that most genes studied to date coalesce in
the Carpathian Mountains of Romania and is dated to African populations points toward the importance of
34,000–36,000 years ago (Trinkaus et al. 2003). Africa as the source of most modern geneticvariation,
Existingdataonhumangeneticvariationsupportand perhaps with some subdivision in the ancestral African
extendconclusionsbasedonthefossilevidence.African population (Satta and Takahata 2002). Sequence data
populations exhibit greater genetic diversity than do for hundreds of locifromwidelydistributedworldwide
populations in the rest of the world, implying that hu- populations eventually may clarify the population pro-
mansappearedfirstinAfricaandlatercolonizedEurasia cesses associated with the appearance of anatomically
and the Americas (Tishkoff and Williams 2002; Yu et modern humans (Wall 2000), as well as the amount of
al.2002;TishkoffandVerrelli2003).Thegeneticvaria- gene flow among modern humans since then.
tionseenoutsideAfricaisgenerallyasubsetofthevaria-
tion within Africa, a pattern that would be producedif
The Distribution of Variation
the migrants from Africa were limited in number and
carriedjustpartofAfricangeneticvariabilitywiththem A thorough description of the differences in patterns
(Cavalli-Sforza and Feldman 2003). Patterns of genetic of genetic variation between humans and other species
variationsuggestanearlierpopulationexpansioninAf- awaits additional genetic studies of human populations
Race,Ethnicity,andGeneticsWorkingGroup:RacialandEthnicCategoriesinGenetics 000
and nonhuman species. But the data gathered to date usedtosituatemanyindividualswithinbroad,geograph-
suggestthathumanvariationexhibitsseveraldistinctive icallybased groupings.Forexample,computeranalyses
characteristics. First, compared with many other mam- ofhundredsofpolymorphiclocisampledingloballydis-
malian species, humans are genetically less diverse—a tributedpopulationshaverevealedtheexistenceofgenetic
counterintuitivefinding,givenourlargepopulationand clusteringthatroughlyisassociatedwithgroupsthathis-
worldwidedistribution(LiandSadler1991;Kaessmann torically have occupied large continental and subconti-
et al. 2001). For example, the chimpanzee subspecies nental regions (Rosenberg et al. 2002; Bamshad et al.
livingjustincentralandwesternAfricahavehigherlev- 2003).
elsofdiversitythandohumans(Ebersbergeretal.2002; Some commentators have argued that these patterns
Yu et al. 2003; Fischer et al. 2004). ofvariationprovideabiologicaljustificationfortheuse
Thedistributionofvariantswithinandamonghuman oftraditionalracialcategories.Theyarguethatthecon-
populationsalsodiffersfromthatofmanyotherspecies. tinentalclusteringscorrespondroughlywiththedivision
Thedetailsofthisdistributionareimpossibletodescribe ofhumanbeingsintosub-SaharanAfricans;Europeans,
succinctly because of the difficulty ofdefininga“popu- western Asians, and northern Africans; eastern Asians;
lation,”theclinalnatureofvariation,andheterogeneity Polynesians and other inhabitants of Oceania; and Na-
across the genome (Long and Kittles 2003). In general, tive Americans(Rischetal.2002).Otherobserversdis-
however, 5%–15% of genetic variation occursbetween agree, saying that the same data undercut traditional
large groups living on different continents, with the re- notionsofracialgroups(KingandMotulsky2002;Cal-
mainingmajorityofthevariationoccurringwithinsuch afell2003;TishkoffandKidd2004).Theypointout,for
groups(Lewontin1972;Jordeetal.2000a;Hindsetal. example,thatmajorpopulationsconsideredracesorsub-
2005).Thisdistributionofgeneticvariationdiffersfrom groups within races do not necessarily form their own
the pattern seen in many other mammalian species,for clusters. Thus, samples taken from India and Pakistan
which existing data suggest greater differentiation be- affiliate with Europeans or eastern Asians rather than
tweengroups(Templeton1998;KittlesandWeiss2003). separatingintoadistinctcluster.However,samplesfrom
Our history as a species also has left genetic signals the Kalash, a small population living in northwestern
inregionalpopulations.Forexample,inadditiontohav- Pakistan, form their own cluster on a level comparable
ing higher levels of genetic diversity, populationsinAf- with those of the major continental regions(Rosenberg
rica tend to have lower amounts of linkage disequilib- et al. 2002).
riumthandopopulationsoutsideAfrica,partlybecause Sampling design can have a critical influence on the
of the larger size of human populations in Africa over resultsofsuchstudies.Studiesofgeneticclusteringoften
thecourseofhumanhistoryandpartlybecausethenum- havereliedonsamplestakenfromwidelyseparatedand
ber of modern humans who left Africa to colonize the socially defined populations. When samples were ana-
rest of the world appears to have been relatively low lyzedfromindividualswhoweremoreevenlydistributed
(Gabrieletal.2002).Incontrast,populationsthathave geographically,clusteringwasfarlessevident(Serreand
undergonedramaticsizereductionsorrapidexpansions Pa¨a¨bo2004).Furthermore,becausehumangeneticvaria-
in the past and populations formed by the mixture of tionisclinal,manyindividualsaffiliatewithtwoormore
previouslyseparateancestralgroupscanhaveunusually continental groups. Thus, the genetically based “bio-
highlevelsoflinkagedisequilibrium(NordborgandTa- geographicalancestry”assignedtoanygivenpersongen-
vare 2002). erallywillbebroadlydistributedandwillbeaccompanied
Many other geographic, climatic, and historicalfac- by sizable uncertainties (Pfaff et al. 2004).
tors have contributed to the patterns of human genetic In many parts of the world, groups have mixed in
variation seen in the world today. For example, popu- such a way that many individualshaverelativelyrecent
lationprocessesassociatedwithcolonization,periodsof ancestors from widely separated regions. Although ge-
geographicisolation,sociallyreinforcedendogamy,and netic analyses of large numbers of loci can produce es-
natural selection all have affected allele frequencies in timatesofthepercentageofaperson’sancestorscoming
certain populations (Jorde et al. 2000b; Bamshad and fromvariouscontinentalpopulations(Shriveretal.2003;
Wooding2003).Ingeneral,however,therecencyofour Bamshadetal.2004),theseestimatesmayassumeafalse
common ancestry and continual gene flow among hu- distinctivenessoftheparentalpopulations,sincehuman
man groups have limited genetic differentiation in our groups have exchanged mates fromlocaltocontinental
species. scales throughout history (Cavalli-Sforza et al. 1994;
Hoerder 2002). Even with large numbers of markers,
Substructure in the Human Population
informationforestimatingadmixtureproportionsofin-
Althoughthegeneticdifferencesamonghumangroups dividualsorgroupsislimited,andestimatestypicallywill
arerelativelysmall,thesedifferencesneverthelesscanbe have wide CIs (Pfaff et al. 2004).
000 Am.J.Hum.Genet.77:000–000,2005
Physical Variation in Humans viduals with certain appearances or from genetic drift
(Roseman 2004).
Thedistributionofmanyphysicaltraitsresemblesthe
distributionofgeneticvariationwithinandbetweenhu- The Social Interpretation of Physical Variation
manpopulations(AmericanAssociationofPhysicalAn-
thropologists 1996; Keita and Kittles 1997). Forexam- The Development of the “Ideology of Race”
ple,∼90%ofthevariationinhumanheadshapesoccurs
withineveryhumangroup,and∼10%separatesgroups, Given our visual acuity and complex social relation-
ships, humans presumably have always observed and
with a greater variability of head shape amongindivid-
speculated about the physical differences among indi-
uals with recent African ancestors (Relethford 2002).
viduals and groups. But different societies have attrib-
Aprominentexceptiontothecommondistributionof
uted markedly different meanings to these distinctions.
physicalcharacteristicswithinandamonggroupsisskin
Classical civilizations from Rome to China tended to
color.Approximately10%ofthevarianceinskincolor
occurswithingroups,and∼90%occursbetweengroups invest much more importancein familyortribalaffilia-
tions than in physical appearance (Diko¨tter 1992; Gol-
(Relethford 2002). This distribution of skin color and
denberg 2003). Some Roman writers adhered to an en-
itsgeographicpatterning—withpeoplewhoseancestors
vironmental determinism in which climate could affect
livedpredominantlyneartheequatorhavingdarkerskin
the appearance and character of groups (Isaac 2004).
than those with ancestors who lived predominantly in
Butinmanyancientcivilizations,individualswithwidely
higher latitudes—indicate that this attribute has been
varying physical appearances could become full mem-
under strong selective pressure. Darker skin appears to
bers of a society by growing up within that society or
be strongly selected for in equatorialregionstoprevent
byadoptingthesociety’sculturalnorms(Snowden1983;
sunburn,skincancer,thephotolysisoffolate,anddam-
Lewis 1990).
age to sweat glands (Sturm et al. 2001; Rees 2003). A
The English word “race” (possibly derived from the
leading hypothesis for the selection of lighter skin in
Spanish raza, meaning “breed” or“stock”),alongwith
higherlatitudesisthatitenablesthebodytoformgreater
many of the ideas now associated with the term, were
amounts of vitamin D, which helps prevent rickets(Ja-
products of the European era of exploration (Smedley
blonski2004).However,thevitaminDhypothesisisnot
1999).AsEuropeansencounteredpeoplefromdifferent
universallyaccepted(Aoki2002),andlighterskininhigh
parts of the world, they speculated about the physical,
latitudesmay correspondsimplytoanabsenceofselec-
social, and cultural differences between human groups.
tion for dark skin (Harding et al. 2000).
TheriseoftheAfricanslavetrade,whichgraduallydis-
Because skin color has been under strong selective
placed an earlier trade in slaves from throughout the
pressure, similar skin colors can resultfromconvergent
world, created a further incentive to categorize human
adaptation rather than from genetic relatedness. Sub-
groups to justify the barbarous treatment of African
Saharan Africans, tribal populations from southern In-
slaves(Meltzer1993).Drawingonclassicalsourcesand
dia, and Australian Aborigines have similar skin pig-
on their own internal interactions—for example, the
mentation,butgeneticallytheyarenomoresimilarthan
hostility between the English and Irish was a powerful
areotherwidelyseparatedgroups.Furthermore,insome
influenceonearlythinkingaboutthedifferencesbetween
partsoftheworldinwhichpeoplefromdifferentregions
people (Takaki 1993)—Europeans began to sort them-
havemixedextensively,theconnectionbetweenskincolor selves and others into groups associated with physical
and ancestry has been substantially weakened (Parra et appearanceandwithdeeplyingrainedbehaviorsandca-
al.2004).InBrazil,forexample,skincolorisnotclosely pacities. A set of “folk beliefs” took hold that linked
associated with the percentage of recent African ances- inherited physical differences between groups to inher-
tors a person has, as estimated from an analysis of ge- itedintellectual,behavioral,andmoralqualities(Banton
netic variants differing in frequency among continent 1977). Although similar ideas can be found in other
groups (Parra et al. 2003). cultures (Lewis 1990; Diko¨tter 1992), they appear not
Considerablespeculationhassurroundedthepossible to have had as much influence on social structures as
adaptive value of other physical features characteristic theydidinEuropeandthepartsoftheworldcolonized
ofgroups,suchastheconstellationoffacialfeaturesob- by Europeans.
servedinmanyeasternandnortheasternAsians(Guthrie In the 18th century, the differences between human
1996). However, any given physical characteristic gen- groups became a focus of scientific investigation (To-
erallyisfoundinmultiplegroups(Lahr1996),anddem- dorov 1993). Initially, scholars focused on cataloging
onstratingthatenvironmentalselectivepressuresshaped and describing “The NaturalVarietiesofMankind,”as
specificphysicalfeatureswillbedifficult,sincesuchfea- Johann Friedrich Blumenbach entitled his 1775 text
tures may have resulted from sexual selection for indi- (which established the five major divisions of humans
Race,Ethnicity,andGeneticsWorkingGroup:RacialandEthnicCategoriesinGenetics 000
still reflected in some racial classifications). But as the Jamaicans to ∼23% for a sample of AfricanAmericans
scienceofanthropologytookshapeinthe19thcentury, from New Orleans (Parra et al. 1998). Similarly, many
European and American scientists increasingly sought people who identify as European American have some
explanations for the behavioraland culturaldifferences African or Native American ancestors, either through
they attributed to groups (Stanton 1960). Forexample, openly interracial marriages or through the gradual in-
theymeasuredtheshapesandsizesofskullsandrelated clusion ofpeoplewithmixedancestryintothemajority
the results to group differences in intelligence or other population. In a survey of college students who self-
attributes (Lieberman 2001). Both before and after the identified as “white” in a northeastern U.S. university,
1859publicationofOntheOriginsofSpecies,adebate ∼30%wereestimatedtohave!90%Europeanancestry
raged in Europe over whether different human groups (Shriver et al. 2003).
had the same origin or were the product of separate In the United States, social and legal conventionsde-
creationsorevolutionarylineages(WolpoffandCaspari veloped over time that forced individuals of mixed an-
1997). cestry into simplified racial categories (Gossett 1997).
Fromthe17ththroughthe19thcenturies,themerging Anexampleisthe“one-droprule”implementedinsome
of folk beliefs about group differenceswithscientificex- state laws that treated anyone with a single known Af-
planationsofthosedifferencesproducedwhatonescholar ricanAmericanancestorasblack(Davis2001).Thede-
has called an “ideology of race” (Smedley 1999). Ac- cennial censuses conducted since 1790 in the United
cording to this ideology, races are primordial, natural, States also created an incentive to establish racial cate-
enduring, anddistinct.Somegroupsmightbetheresult goriesandfitpeopleintothosecategories(Nobles2000).
of mixture between formerly distinct populations, but InothercountriesintheAmericaswheremixingamong
carefulstudycandistinguishtheancestralracesthathad groupswasmoreextensive,socialcategorieshavetended
combined to produce admixed groups. tobemorenumerousandfluid,withpeoplemovinginto
The concept of race found wide application in many or out of categories on the basis of a combination of
societies. The eugenics movement of the late 19th and socioeconomicstatus,socialclass,ancestry,andappear-
early20thcenturiesassertedasself-evidentthebiological ance (Mo¨rner 1967).
inferiority of particular groups (Kevles 1985). In many Efforts to sort the increasingly mixed population of
parts of the world, the idea of race became a way of theUnitedStatesintodiscretecategoriesgeneratedmany
rigidlydividinggroupsbyuseofcultureaswellasphysi- difficulties(Spickard1992).Bythestandardsusedinpast
cal appearances (Hannaford 1996). Campaigns of op- censuses, many millions of children born in the United
pression and genocide often used supposed racial differ- States have belonged to a different race than have one
encestomotivateinhumanactsagainstothers(Horowitz of their biological parents. Efforts to track mixing be-
2001). tween groups led to a proliferation of categories (such
as “mulatto” and “octoroon”) and “blood quantum”
distinctions that became increasingly untethered from
The Incongruities of Racial Classifications
self-reported ancestry. A person’s racial identity can
Even as the idea of “race” was becoming a powerful changeovertime,andself-ascribedracecandifferfrom
organizingprincipleinmanysocieties,theshortcomings assigned race (Kressin et al. 2003). Until the 2000 cen-
of the concept were apparent. In the Old World, the sus, Latinos were required toidentifywithasinglerace
gradual transition in appearances from one group to despite the long history of mixing in Latin America;
adjacent groups emphasized that “one variety of man- partly as a result of the confusion generated by thedis-
kinddoessosensiblypassintotheother,thatyoucannot tinction,42%ofLatinorespondentsinthe2000census
mark outthelimitsbetweenthem,”asBlumenbachob- ignoredthespecifiedracialcategoriesandchecked“some
servedinhiswritingsonhumanvariation(Marks1995, other race” (Mays et al. 2003).
p.54).InpartsoftheAmericas,thesituationwassome-
whatdifferent.TheimmigrantstotheNewWorldcame
largelyfromwidelyseparatedregionsoftheOldWorld— Ethnicity as a Way of Categorizing People
westernandnorthernEurope,westernAfrica,and,later,
eastern Asia and southern Europe. In theAmericas,the Astheproblemssurroundingtheword“race”became
immigrantpopulationsbegantomixamongthemselves increasinglyapparentduringthe20thcentury,theword
andwiththeindigenousinhabitantsofthecontinent.In “ethnicity”waspromotedasawayofcharacterizingthe
the United States, for example, most people who self- differencesbetweengroups(HuxleyandHaddon1936;
identify as African American have some European an- HutchinsonandSmith1996).Ethnicitytypicallyempha-
cestors—in one analysis of genetic markers that have sizesthecultural,socioeconomic,religious,andpolitical
differing frequencies between continents, European an- qualities of human groups rather than their genetican-
cestry ranged from an estimated 7% for a sample of cestry. It may encompass language, diet, religion,dress,
000 Am.J.Hum.Genet.77:000–000,2005
customs,kinshipsystems,orhistoricalorterritorialiden- has limitations as a way of categorizing people (Elliott
tity (Cornell and Hartmann 1998). and Brodwin 2002). When asked about the ancestryof
However, as a way of understanding human groups, theirparentsandgrandparents,manypeoplecannotpro-
ethnicity also suffers from several shortcomings. First, vide accurate answers. In one series of focus groups in
ascribinganethnicidentitytoagroupcanimplyamuch thestateofGeorgia,40%of∼100respondentssaidthey
greaterdegreeofuniformitythanisactuallythecase.In did not know one or more of their four grandparents
theUnitedStates,theethnicgroup“HispanicorLatino” wellenoughtobecertainhowthatperson(s)wouldiden-
containssuchsubgroupsasCubanAmericans,Mexican tifyracially(Conditetal.2003).Misattributedpaternity
Americans, Puerto Ricans, and recent immigrantsfrom oradoptioncanseparatebiogeographicalancestryfrom
CentralAmerica(Hayes-BautistaandChapa1987).Com- sociallydefinedancestry.Furthermore,theexponentially
biningthesegroupsintoasinglecategorymayserveuse- increasing number of our ancestors makes ancestry a
fulbureaucraticorpoliticalendsbutdoesnotnecessarily quantitativeratherthanqualitativetrait—5centuries(or
result in a better understanding of these groups. 20generations)ago,eachpersonhadamaximumof11
Also, ethnicity, like race, is a malleable concept that million ancestors (Ohno 1996). To complicate matters
can change dramatically in different times or circum- further, recent analyses suggest that everyone living to-
stances(Waters1990;Smelseretal.2001).Ethnicgroups day has exactly the same set of genealogical ancestors
may come into existence and then dissipate as a result who lived as recently as a few thousand years in the
of broad historical or social trends. Individuals might past, although we have received ourgeneticinheritance
change ethnic groups over the course of their lives or in different proportions fromthoseancestors(Rohdeet
identify with more than one group. A researcher, clini- al. 2004).
cian,orgovernmentofficialmightassignanethnicityto In the end, the terms “race,” “ethnicity,” and “an-
an individual quite different from the one that person cestry”alldescribejustasmallpartofthecomplexweb
would acknowledge (Kressin et al. 2003). ofbiologicalandsocialconnectionsthatlinkindividuals
Finally,despiteattemptstodistinguish“ethnicity”from and groups to each other.
“race,” the two terms often are used interchangeably
(Oppenheimer 2001). Ethnic groups can share a belief Racial, Ethnic, and Ancestral Categories in Genetics
in a common ancestral origin (Cornell and Hartmann Research
1998), which also can be a defining characteristic of a
racial group. Furthermore, ethnic groups tend to pro-
The Effects of Racial and Ethnic Identities on Health
mote marriage within the group, which creates an ex-
pectation of biological cohesion regardless of whether Racial and ethnic groups can exhibit substantial av-
that cohesion existed in the past. erage differences in disease incidence, disease severity,
disease progression, and responseto treatment(LaVeist
2002). In the United States, African Americans have
Ancestry as a Way of Categorizing People
higher rates of mortality than does any other racial or
Analternativetotheuseofracialorethniccategories ethnic group for 8 of the top 10 causesofdeath(Hum-
in genetics research is to categorizeindividualsinterms meretal.2004).U.S.Latinoshavehigherratesofdeath
ofancestry.Ancestrymaybedefinedgeographically(e.g., fromdiabetes,liverdisease,andinfectiousdiseasesthan
Asian,sub-SaharanAfrican,ornorthernEuropean),geo- donon-Latinos(VegaandAmaro1994).NativeAmeri-
politically (e.g., Vietnamese, Zambian, or Norwegian), cans suffer from higher rates of diabetes, tuberculosis,
or culturally (e.g., Brahmin, Lemba, or Apache). The pneumonia,influenza,andalcoholismthandoestherest
definition of ancestry may recognize a single predomi- of the U.S. population (Mahoney and Michalek 1998).
nantsourceormultiplesources.Ancestrycanbeascribed European Americans die more often from heart disease
to an individual by an observer, as was the case with andcancerthandoNativeAmericans,AsianAmericans,
the U.S. census prior to 1960; it can beidentifiedbyan or Hispanics (Hummer et al. 2004).
individualfromalistofpossibilitiesorwithuseofterms Considerable evidence indicates that the racial and
drawn from that person’s experience; or it can be cal- ethnic health disparities observed in the United States
culated from genetic data by use of loci with allele fre- arise mostly through the effects of discrimination, dif-
quencies that differ geographically, as described above. ferences in treatment, poverty, lack of access to health
Atleastamongthoseindividualswhoparticipateinbio- care, health-related behaviors, racism, stress, and other
medical research, genetic estimates of biogeographical socially mediated forces. The infant mortality rate for
ancestrygenerallyagreewithself-assessedancestry(Tang African Americans is approximately twice the rate for
et al. 2005), but in an unknown percentage of cases, EuropeanAmericans,but,inastudythatlookedatmem-
they do not (Brodwin 2002; Kaplan 2003). bers of these two groups who belonged to the military
Despite its seemingly objective nature, ancestry also andreceivedcarethroughthesamemedicalsystem,their
Race,Ethnicity,andGeneticsWorkingGroup:RacialandEthnicCategoriesinGenetics 000
infant mortality rates were essentiallyequivalent(Raw- variants present in the ancestral population before the
lings and Weir 1992). Recent immigrants to theUnited dispersalofmodernhumansfromAfricaplayanimpor-
StatesfromMexicohavebetterindicatorsonsomemea- tantroleinhumandiseases(GoldsteinandChikhi2002).
sures of health than do Mexican Americans who are GeneticvariantsassociatedwithAlzheimerdisease,deep
more assimilated into American culture (Franzini et al. venous thrombosis, Crohn disease, and type 2 diabetes
2001). Diabetes and obesity are more common among appeartoadheretothismodel(Lohmuelleretal.2003).
NativeAmericanslivingonU.S.reservationsthanamong However, the generality of the model has not yet been
those living outside reservations (Cooper et al. 1997). established and, in some cases, is in doubt (Weiss and
RatesofheartdiseaseamongAfricanAmericansareas- Terwilliger2000;PritchardandCox2002;Cardonand
sociated with the segregation patterns in the neighbor- Abecasis 2003). Some diseases, such as many common
hoods where they live (Fang et al. 1998). Furthermore, cancers,appearnottobewelldescribedbythecommon
the risks for many diseases are elevated for socially,ec- disease/commonvariantmodel(KittlesandWeiss2003;
onomically, and politically disadvantaged groups inthe Wiencke 2004).
United States, suggesting that socioeconomic inequities Another possibility is that common diseases arise in
are the root causes of most of the differences (Cooper partthroughtheactionofcombinationsofvariantsthat
et al. 2003; Cooper 2004). areindividuallyrare(Pritchard2001;Cohenetal.2004).
However, differences in allele frequencies certainly Mostofthedisease-associatedallelesdiscoveredtodate
contributetogroupdifferencesintheincidenceofsome have been rare, and rare variants are more likely than
monogenic diseases, and they may contribute to differ- common variants to be differentiallydistributedamong
ences in the incidence of some common diseases(Risch groupsdistinguishedbyancestry(Rischetal.2002;Kit-
et al. 2002; Burchard et al. 2003; Tate and Goldstein tles and Weiss 2003). However, groups could harbor
2004). For the monogenic diseases, the frequency of different, though perhapsoverlapping,setsofrarevari-
causative alleles usually correlates best with ancestry, ants, which would reduce contrasts between groups in
whether familial (for example, Ellis–van Creveld syn- the incidence of the disease.
drome among the Pennsylvania Amish), ethnic (Tay- Thenumber ofvariantscontributingtoadiseaseand
Sachs diseaseamongAshkenaziJewishpopulations),or the interactions among those variants also could influ-
geographical (hemoglobinopathies among people with encethedistributionofdiseasesamonggroups.Thedif-
ancestors who lived in malarial regions). To the extent ficultythathasbeenencounteredinfindingcontributory
that ancestry corresponds with racial or ethnic groups alleles for complex diseases and in replicating positive
or subgroups, the incidence of monogenic diseases can associations suggests that many complex diseases in-
differ between groups categorized by race or ethnicity, volvenumerousvariantsratherthanamoderatenumber
andhealth-careprofessionalstypicallytakethesepatterns of alleles, and the influence of any given variant may
into account in making diagnoses. dependincriticalwaysonthegeneticandenvironmental
Even with common diseases involving numerous ge- background (Risch 2000; Weiss and Terwilliger 2000;
netic variants and environmental factors, investigators Altmu¨ller et al. 2001; Hirschhorn et al. 2002). If many
point to evidence suggesting the involvement of differ- allelesarerequiredtoincreasesusceptibilitytoadisease,
entiallydistributedalleleswithsmalltomoderateeffects. the odds are low that the necessary combination of al-
Frequently cited examples include hypertension(Doug- leles would become concentrated in a particular group
las et al. 1996), diabetes (Gower et al. 2003), obesity purely through drift (Cooper 2004).
(Fernandezetal.2003),andprostatecancer(Platzetal.
2000). However, in none of these caseshasallelicvaria-
Population Substructure in Genetics Research
tion in a susceptibility gene been shown to account for
a significant fraction of the difference in disease preva- Oneareainwhichracialandethniccategoriescanbe
lence among groups, and the role of genetic factors in important considerations in genetics research is in con-
generating these differences remains uncertain (Moun- trolling for confounding between population substruc-
tain and Risch 2004). ture,environmentalexposures,andhealthoutcomes.As-
sociation studies can produce spurious results if cases
and controls have differing allele frequencies for genes
The Allelic Architecture of Disease
thatarenotrelatedtothediseasebeingstudied(Cardon
Thegeneticarchitectureofcommondiseasesisanim- and Palmer 2003; Marchini et al. 2004), although the
portant factor in determining the extent to which pat- magnitudeofthisproblemingeneticassociationstudies
terns of genetic variation influence group differencesin issubjecttodebate(ThomasandWitte2002;Wacholder
healthoutcomes(ReichandLander2001;Pritchardand et al. 2002). Various methods have been developed to
Cox 2002; Smith and Lusis 2002). According to the detectandaccountforpopulationsubstructure(Morton
commondisease/commonvarianthypothesis,common andCollins1998;Hoggartetal.2003),butthesemeth-
000 Am.J.Hum.Genet.77:000–000,2005
odscanbedifficulttoapplyinpractice(Freedmanetal. economic,social,andpsychologicalexperiencesandcan
2004). be exposed to very different environments as a conse-
Populationsubstructurealsocanbeusedtoadvantage quenceoftheirmembershipinaparticulargroup.These
ingeneticassociationstudies.Forexample,populations differentialexperiencesandenvironmentalexposurescan
that represent recent mixtures of geographically sepa- be used to investigate the biological mechanisms that
rated ancestral groups can exhibit longer-range linkage contribute to health disparities among groups (LaVeist
disequilibriumbetweensusceptibilityallelesandgenetic 1996). In addition, self-identified race, ethnicity, or
markersthanisthecaseforotherpopulations(Hoggart ancestry can provide measures of population substruc-
et al. 2004; Patterson et al. 2004; Smith et al. 2004; ture that help avoid false-positiveresultsinassociation
McKeigue2005).Geneticstudiescanusethisadmixture studies.
linkage disequilibrium to search for disease alleleswith Onewayforgeneticiststoeasethedilemmatheyface
fewer markers than would be needed otherwise. Asso- istotrytomovebeyondracial,ethnic,orancestralcate-
ciationstudiesalsocantakeadvantageofthecontrasting gories in their work (Ota Wang and Sue 2005; Shields
experiencesofracialorethnicgroups,includingmigrant et al. 2005). Rather than using racial, ethnic,orances-
groups,tosearchforinteractionsbetweenparticularal- tral labels as proxies for much more detailed social,
leles and environmental factors that might influence economic,environmental,biological,orgeneticfactors,
health (Chaturvedi 2001; Collins et al. 2003). researcherscantrytomeasurethesefactorsdirectly.For
example,controllingforsocioeconomicstatusbyuseof
Conclusions census tract data can substantially reduce the excess
mortalityriskobservedindisadvantagedminoritypopu-
When deciding whether and how to use racial, ethnic, lations (Krieger et al. 2005). Similarly, genotyping to
andancestralcategoriesinresearch,geneticistsfacecon- estimate biogeographical ancestry can be a better con-
flictingdemands.Ontheonehand,manyobservershave trolforpopulationsubstructurethanself-identifiedrace,
made powerful arguments in favor of reducing or even ethnicity, or ancestry (Shields et al. 2005).
eliminating the use of racial or ethnic categories in ge- Whentheuseofracialorethniccategoriesinresearch
netics research (Fullilove 1998; Goodman 2000; Lee et is deemed necessary, researchers can avoid overgener-
al.2001;Braun2002;Duster2003,2005;Stevens2003; alizationbyusinglabelsthatareasspecificaspossible.
Kahn 2004; Sankar et al. 2004; Ossorio and Duster Todaymanygeneticinvestigationslabelpopulationswith
2005). These observerspoint out thattheuseofthese the same loose terms used by the public (Sankar and
categories reinforces the widespread impression that Cho 2002; Clayton 2003; Collins 2004; Comstock et
health inequities arise throughtheactionofgeneticdif- al. 2004). But labels such as “Hispanic,” “Black,”
ferences and independent of socially mediated mecha- “MexicanAmerican,”“White,”“Asian,”“European,”
nisms. In this way, genetics research that involvesmak- or “African” can have ambiguous or contradictory
ingpopulationcomparisonscaninaccuratelystereotype meaningsamongresearchers,researchsubjects,andthe
racial and ethnic groups, both by implying that such generalpublic.Useofsuchbroadlabelswithoutcareful
groups are clearly delineated and by associating health definitions can impair scientific understanding and im-
outcomeswithallindividualsinthosegroupsratherthan ply that distinctions between socially defined popula-
with only those individuals who exhibit the outcome. tionsaregeneticallywellestablished.Geneticsresearch-
Furthermore, according to critics, an overemphasis on ers often rely on the categories specified in the U.S.
thegeneticcomponentofhealthdifferencesshiftsatten- census—encouraged by regulations that urge diversity
tion and resources away from established contributors of study populations—butthesecategoriesareusedto-
to health disparities—in particular, the differences in day mainly for administrative and social purposes and
treatmentandsocioeconomicdisadvantagesthatdispro- werenotdesignedforgeneticsresearch.Evenwhenthe
portionatelyaffectminoritygroups(Sankaretal.2004). census categories are used to select researchsubjectsto
Geneticsresearchoffersnoevidencethatanyonegroup ensure diversity, researchers can analyze their results
is superior or inferior to any other, although some in- using more-specific labels that are closely tied to the
dividuals continue to try to distort genetic findings to scientific questions being asked (Kaplan and Bennett
buttress prejudiced outlooks. Biomedical research that 2003). For example, labels based on biogeographical
accentuatesgeneticdifferencesamonggroups,saycritics ancestry may be suited for many genetics studies, so-
of this research, is as conceptually flawed as the race cially based labels may be more appropriate for health
science of the 19th century (Bhopal 1997). disparities and clinical research, and both types of in-
Ontheotherhand,raceandethnicityaresuchprom- formation may be valuable for studies of some gene-
inent aspects of many societies that it is difficult, and environment interactions.
often inadvisable, to ignore them in genetics research. Individualscanbeassignedtospecificpopulationcat-
Themembersofthesegroupscanhavewidelydisparate egoriesinanumberofways,withthemostappropriate
Race,Ethnicity,andGeneticsWorkingGroup:RacialandEthnicCategoriesinGenetics 000
way, again, depending on the research question being son2004),obesity(CalleandKaaks2004),exposureto
investigated(FosterandSharp2004;InternationalHap- toxins(Whyattetal.2004),stress(Wallaceetal.2004),
MapConsortium2004).Researchsubjectscanbeasked and other factors influence later illnesseshighlightsthe
to identify themselves with geographical or cultural multipleinterconnectionsamongbiologicalmechanisms,
populations,whichmaybedefinedbytheresearcheror environmental influences, and chance events (Shostak
by the local communities within which the research is 2003).
being conducted. Communities and researchers can Despite this complexity, genetics researchers have a
choosecategoriestogetherthroughaconsultativeoren- unique opportunity to reduce at least some of the con-
gagementprocessbetweenresearchersandthecommu- fusion and controversy surrounding the issues of race,
nity(Fosteretal.1999;Conditetal.2002).Categorical ethnicity, ancestry, and health. They can demonstrate
systemsalsocanincludethepossibilityofsimultaneous, the irrelevance of racial and ethnic labels for pursuing
multiple-groupmembershipsingroupsathigherorlower many research questions and health improvement ob-
levels of organization. jectives—for example, by clarifying the many ways in
A number of journals, including Nature Genetics which environmental factorsthatextendacrossgroups
(Anonymous 2000), Archives of Pediatrics & Adoles- interact with biological processes to produce common
centMedicine(RivaraandFinberg2001),andtheBrit- diseases (Lin and Kelsey 2000; Rotimi 2004). By em-
ishMedicalJournal(Anonymous1996),haveseparately phasizing the close genetic affinities between members
issued guidelines stating that researchers should care- of different groups, researchers can reduce the wide-
fullydefinethetermstheyuseforpopulations,andsome spreadmisconceptionthatsubstantialgeneticdifferences
journals have asked researchers to justify their use of separategroups(Wilsonetal.2001;Olson2002;Jorde
racial or ethnic groups in research. But enforcementof and Wooding 2004). As the complex originsofhuman
these guidelines has been uneven, and compliance will traits,behaviors,anddiseasesslowlyareunraveled,how
continuetobespottywithoutgreaterawarenessamong genetics research is conducted could influence whether
researchers of the difficulties and risks involved in de- racial and ethnic discrimination increases or decreases
finingpopulations(SankarandCho2002;Anonymous over time.
2004).
Efforts to move past the useof racialandethniccat-
Acknowledgments
egories in genetics research often will require consid-
eration of a very broad range of additional variables The Race, Ethnicity, and Genetics Working Group of the
(Chakravarti and Little2003).Thesevariableswilldif- National Human Genome Research Institute appreciates the
fer from study to study, but even a partial list includes valuable input received on earlier drafts of this paper from
racismanddiscrimination,socioeconomicstatus,social Michael Bamshad, Wylie Burke, Mildred Cho, Troy Duster,
class, personal or family wealth, environmental expo- SaraHull,LynnJorde,JeffLong,JeffMurray,andKenWeiss.
sures, insurance status, age, diet and nutrition, health
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