Abstract
The admixture of different ancestral populations in America may have important implications for the risk for psychiatric disorders, as it appears to have for other medical disorders. The present study investigated the role of population admixture in risk for several psychiatric disorders in European-Americans (EAs) and African-Americans (AAs). This is a multisite study with 3,792 subjects recruited from across the United States, including 3,119 EAs and 673 AAs. These subjects included healthy controls and those with substance dependence (SD) [including alcohol dependence (AD), cocaine dependence, and opioid dependence], social phobia, affective disorders, and schizophrenia. In addition, DNA was included from 78 West Africans. The degree of admixture for each subject was estimated by analysis of a set of ancestry-informative genetic markers using the program STRUCTURE, and was compared between cases and controls. As noted previously, the degree of admixture in AAs was higher than EAs. In EAs, the degree of admixture (with African ancestry) was significantly lower in patients with SD (mainly AD) than controls (P = 0.009 for SD; P = 0.008 for AD). This finding suggests that population admixture may modulate risk for alcohol dependence. Population admixture might protect against alcohol dependence by increasing average heterozygosity and reducing the risk of deleterious recessive alleles. We cannot exclude the possibility that the results might have been influenced by selection bias due to the multisite nature of the study.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, revised. American Psychiatric Press, Washington
American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press, Washington, DC
Blouin AG, Perez EL, Blouin JH (1988) Computerized administration of the diagnostic interview schedule. Psychiatry Res 23:335–344
Brutsaert TD, Parra EJ, Shriver MD, Gamboa A, Rivera-Ch M, Leon-Velarde F (2005) Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives. Am J Physiol Regul Integr Comp Physiol 289:R225–R234
Chakraborty R, Weiss KM (1986) Frequencies of complex diseases in hybrid populations. Am J Phys Anthropol 70:489–503
Degenhardt L, Bohnert KM, Anthony JC (2008) Assessment of cocaine and other drug dependence in the general population: “gated” versus “ungated” approaches. Drug Alcohol Depend 93:227–232
Fernandez JR, Shriver MD, Beasley TM, Rafla-Demetrious N, Parra E, Albu J et al (2003) Association of African genetic admixture with resting metabolic rate and obesity among women. Obes Res 11:904–911
Gelernter J, Panhuysen C, Weiss R, Brady K, Hesselbrock V, Rounsaville B et al (2005) Genomewide linkage scan for cocaine dependence and related traits: significant linkages for a cocaine-related trait and cocaine-induced paranoia. Am J Med Genet B Neuropsychiatr Genet 136B:45–52
Goncalves VF, Prosdocimi F, Santos LS, Ortega JM, Pena SD (2007) Sex-biased gene flow in African Americans but not in American Caucasians. Genet Mol Res 6:156–161
Hammer MF, Chamberlain VF, Kearney VF, Stover D, Zhang G, Karafet T et al (2006) Population structure of Y chromosome SNP haplogroups in the United States and forensic implications for constructing Y chromosome STR databases. Forensic Sci Int 164:45–55
Hanis CL, Chakraborty R, Ferrell RE, Schull WJ (1986) Individual admixture estimates: disease associations and individual risk of diabetes and gallbladder disease among Mexican-Americans in Starr County, Texas. Am J Phys Anthropol 70:433–441
Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG et al (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72:1492–1504
Hunley KL, Healy ME, Long JC (2009) The global pattern of gene identity variation reveals a history of long-range migrations, bottlenecks, and local mate exchange: Implications for biological race. Am J Phys Anthropol (epub ahead of print)
Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH et al (2004) Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci U S A 101:17316–17321
Klimentidis YC, Miller GF, Shriver MD (2009) The relationship between European genetic admixture and body composition among Hispanics and Native Americans. Am J Hum Biol (epub ahead of print)
Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC et al (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310:1782–1786
Lind JM, Hutcheson-Dilks HB, Williams SM, Moore JH, Essex M, Ruiz-Pesini E et al (2007) Elevated male European and female African contributions to the genomes of African American individuals. Hum Genet 120:713–722
Luo X, Klempan TA, Lappalainen J, Rosenheck RA, Charney DS, Erdos J et al (2004) NOTCH4 gene haplotype is associated with schizophrenia in African Americans. Biol Psychiatry 55:112–117
Luo X, Kranzler HR, Zuo L, Wang S, Blumberg HP, Gelernter J (2005a) CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study. Hum Mol Genet 14:2421–2434
Luo X, Kranzler HR, Zuo L, Yang BZ, Lappalainen J, Gelernter J (2005b) ADH4 gene variation is associated with alcohol and drug dependence: results from family controlled and population-structured association studies. Pharmacogenet Genomics 15:755–768
McKeigue PM (1998) Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture. Am J Hum Genet 63:241–251
McLean DC Jr, Spruill I, Gevao S, Morrison EY, Bernard OS, Argyropoulos G et al (2003) Three novel mtDNA restriction site polymorphisms allow exploration of population affinities of African Americans. Hum Biol 75:147–161
Molokhia M, Hoggart C, Patrick AL, Shriver M, Parra E, Ye J et al (2003) Relation of risk of systemic lupus erythematosus to West African admixture in a Caribbean population. Hum Genet 112:310–318
Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R et al (1998) Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 63:1839–1851
Parra EJ, Kittles RA, Argyropoulos G, Pfaff CL, Hiester K, Bonilla C et al (2001) Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina. Am J Phys Anthropol 114:18–29
Pierucci-Lagha A, Gelernter J, Feinn R, Cubells JF, Pearson D, Pollastri A et al (2005) Diagnostic reliability of the semi-structured assessment for drug dependence and alcoholism (SSADDA). Drug Alcohol Depend 80:303–312
Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959
Project MATCH Research Group (1998) Matching alcoholism treatments to client heterogeneity: treatment main effects and matching effects on drinking during treatment. Project MATCH Research Group. J Stud Alcohol 59:631–639
Reid DD (1971) The future of migrant studies. Isr J Med Sci 7:1592–1596
Reiner AP, Ziv E, Lind DL, Nievergelt CM, Schork NJ, Cummings SR et al (2005) Population structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study. Am J Hum Genet 76:463–477
Reiner AP, Carlson CS, Ziv E, Iribarren C, Jaquish CE, Nickerson DA (2007) Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study. Hum Genet 121:565–575
Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA et al (2002) Genetic structure of human populations. Science 298:2381–2385
Rosenberg NA, Li LM, Ward R, Pritchard JK (2003) Informativeness of genetic markers for inference of ancestry. Am J Hum Genet 73:1402–1422
Rosenberg NA, Mahajan S, Ramachandran S, Zhao C, Pritchard JK, Feldman MW (2005) Clines, clusters, and the effect of study design on the inference of human population structure. PLoS Genet 1:e70
Rosenheck R, Cramer J, Xu W, Thomas J, Henderson W, Frisman L et al (1997) A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. N Engl J Med 337:809–815
Roth W (2005) The end of the one-drop rule? Labeling of multiracial children in black intermarriages. Sociol Forum 20:35–67
Rounsaville BJ, Bryant K, Babor T, Kranzler H, Kadden R (1993) Cross system agreement for substance use disorders: DSM-III-R, DSM-IV and ICD-10. Addiction 88:337–348
Singleton-Bowie SM (1995) The effect of mental health practitioners’ racial sensitivity on African Americans’ perceptions of service. Soc Work Res 19:238–244
Smith MW, Lautenberger JA, Shin HD, Chretien JP, Shrestha S, Gilbert DA et al (2001) Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. Am J Hum Genet 69:1080–1094
Spitzer R, Endicott J (1975) Schedule for affective disorders and schizophrenia: lifetime version. New York Biometrics Research Division. New York State Psychiatric Institute, New York
Spitzer RL, Williams JB, Gibbon M, First MB (1992) The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry 49:624–629
Stein MB, Schork NJ, Gelernter J (2004) A polymorphism of the beta1-adrenergic receptor is associated with low extraversion. Biol Psychiatry 56:217–224
Waters MC (1991) The role of lineage in identity formation among black Americans. Qual Sociol 14:57–76
Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447:661–678
Williams D (1995) African American mental health: persisting questions and paradoxical findings. Afr Am Res Perspect 2:8–16
Yang BZ, Zhao H, Kranzler HR, Gelernter J (2005) Practical population group assignment with selected informative markers: characteristics and properties of Bayesian clustering via STRUCTURE. Genet Epidemiol 28:302–312
Acknowledgments
Ann Marie Lacobelle and Greg Kay provided excellent technical assistance. Thomas Hudak, Ellen Koucky, Michelle McKain, Michelle Slivinsky, Konstantin Voronin and Carolyn Wenner assisted with patient interviews. This work was supported in part by National Institute on Drug Abuse (NIDA) grants R01-DA12849, R01-DA12690, K24-DA15105, and DA020709, National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01-AA11330, R01-AA016015, P50-AA12870, P50-AA03510, K24-AA13736, R01-AA015615 and K05-AA14906, National Institute on Mental Health grants R01-MH43775 and R01-MH70902, National Center for Research Resources (NCRR) grant M01-RR06192, Alcoholic Beverage Medical Research Foundation (ABMRF) grant award R06932 (X. Luo); and by the U.S. Department of Veterans Affairs (the VA Alcohol Research Center, the VA Medical Research Program, the VA Connecticut–Massachusetts Mental Illness Research, Education and Clinical Center [MIRECC], and the VA Research Enhancement Award Program [REAP] research center). Drs. Mark D. Shriver and Robert Rosenheck provided some of the DNA samples. We thank the Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia (members of the study group are listed in Rosenheck et al. (1997) and some investigators from Project MATCH, a collaborative clinical trial sponsored by NIAAA, who provided phenotypic data and blood samples for DNA extraction and genotyping.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zuo, L., Luo, X., Listman, J.B. et al. Population admixture modulates risk for alcohol dependence. Hum Genet 125, 605–613 (2009). https://doi.org/10.1007/s00439-009-0647-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-009-0647-4