Behavior Genetics

, Volume 45, Issue 2, pp 255–261 | Cite as

Population Frequencies of the Triallelic 5HTTLPR in Six Ethnicially Diverse Samples from North America, Southeast Asia, and Africa

  • Brett C. HaberstickEmail author
  • Andrew Smolen
  • Redford B. Williams
  • George D. Bishop
  • Vangie A. Foshee
  • Terence P. Thornberry
  • Rand Conger
  • Ilene C. Siegler
  • Xiaodong Zhang
  • Jason D. Boardman
  • Zygmunt Frajzyngier
  • Michael C. Stallings
  • M. Brent Donnellan
  • Carolyn T. Halpern
  • Kathleen Mullan Harris
Brief Communication


Genetic differences between populations are potentially an important contributor to health disparities around the globe. As differences in gene frequencies influence study design, it is important to have a thorough understanding of the natural variation of the genetic variant(s) of interest. Along these lines, we characterized the variation of the 5HTTLPR and rs25531 polymorphisms in six samples from North America, Southeast Asia, and Africa (Cameroon) that differ in their racial and ethnic composition. Allele and genotype frequencies were determined for 24,066 participants. Results indicated higher frequencies of the rs25531 G-allele among Black and African populations as compared with White, Hispanic and Asian populations. Further, we observed a greater number of ‘extra-long’ (‘XL’) 5HTTLPR alleles than have previously been reported. Extra-long alleles occurred almost entirely among Asian, Black and Non-White Hispanic populations as compared with White and Native American populations where they were completely absent. Lastly, when considered jointly, we observed between sample differences in the genotype frequencies within racial and ethnic populations. Taken together, these data underscore the importance of characterizing the L-G allele to avoid misclassification of participants by genotype and for further studies of the impact XL alleles may have on the transcriptional efficiency of SLC6A4.


5HTTLPR Serotonin transporter rs25531 Hispanics Add health Population genetics Cameroon 



This research uses data from the National Longitudinal Study of Adolescent to Adult Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and K.M.H. at the University of North Carolina at Chapel Hill, and funded by Grant P01 HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the National Longitudinal Study of Adolescent Health data files is available on the National Longitudinal Study of Adolescent to Adult Health Web site ( This research was also supported by Grants R01-HD057222 (Genes in Context Study); R01-DA020195 (Rochester Youth Development Study); R-581-000-117-101, R-581-000-099, R-581-000-090-101, R-581-000-083-101 and R-581-000-062-112 (Singapore Cardiovascular Study); P01-HD064687 (Family Transitions Project); 2P01-HL036587 to RBW and ICS; and the University of Colorado Butcher Foundation (Cameroon Sample).

Financial disclosures and Conflict of interest statement

Redford Williams holds a U.S. patent on 5HTTLPR L allele as a risk marker for CVD in persons exposed to chronic stress. Redford Williams is a founder and major stockholder in Williams LifeSkills, Inc., a company that develops, tests and markets behavioral products for stress and anger management.

Human and Animal Rights and Informed Consent

Written informated consent was obtained during each of the six studies utilizing Institutional Review Board approved protocols by the their respective Universities. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants for being included in the study.

Supplementary material

10519_2014_9703_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 30 kb)


  1. Anchordoquy HC, McGeary C, Liu L, Krauter KS, Smolen A (2003) Genotyping of three candidate genes after whole-genome preamplification of DNA collected from buccal cells. Behav Genet 33:73–78CrossRefPubMedGoogle Scholar
  2. Bryc K, Velez C, Karafet T, Moreno-Estrada A, Reynolds A, Auton A, Hammer M, Bustamante CD, Ostrer H (2010) Genome-wide patters of population structure and admixture among Hispanic/Latino populations. Proc Natl Acad Sci USA 107(S2):8954–8961CrossRefPubMedCentralPubMedGoogle Scholar
  3. Conger RD, Scholfield TJ, Neppi TK (2012) Intergenerational continuity and discontinuity in harsh parenting. Parent Sci Pract 12(2–3):222–231Google Scholar
  4. Don RH, Cox RT, Wainwright BJ, Baker K, Mattick JS (1992) “Touchdown” PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res 19:4008CrossRefGoogle Scholar
  5. Foshee VA, Benefield TS, Puvanesarajah S, Reyes HL, Haberstick BC, Smlen A, Ennett ST, Suchindran C (2014) Self-regulatory failure and the perpetration of adolescent dating violence: examining an alcohol use by gene explanation. Aggress Behav Epub ahead of print. doi: 10.1002/ab.21550
  6. Gelernter J, Kranzler H, Cubells JF (1997) Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibrium in African- and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 101:243–246CrossRefPubMedGoogle Scholar
  7. Genovese G, Handsaker RE, Li H, Kenny EE, McCarroll SA (2013) Mapping the human heference Genome’s missing sequence by three-way admixture in Latino genomes. Am J Hum Genet 93:411–421CrossRefPubMedCentralPubMedGoogle Scholar
  8. Goldman N, Glei DA, Lin YH, Weinstein M (2010) The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms. Depress Anxiety 27:260–269CrossRefPubMedCentralPubMedGoogle Scholar
  9. Haberstick BC, Smolen A, Stetler GL, Tabor JW, Roy T, Casey RH, Roy F, Ryals LA, Hewitt C, Whitsel EA, Halpern CT, Killeya-Jones LA, Lessem JM, Hewitt JK, Harris KM (2014) Simple sequence repeats in the National Longitudinal Study of Adolescent Health: an ethnically diverse resource for genetic analysis of health and behavior. Behav Genet 44:487–497CrossRefPubMedCentralPubMedGoogle Scholar
  10. Harris KM, Halpern CT, Haberstick BC, Smolen A (2013) The National Longitudinal Study of Adolescent Health (Add Health) sibling pairs data. Twin Res Hum Genet 16:391–398CrossRefPubMedCentralPubMedGoogle Scholar
  11. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of the human serotonin transporter gene expression. J Neurochem 66:2621–2624CrossRefPubMedGoogle Scholar
  12. Hu X, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 78:815–826CrossRefPubMedCentralPubMedGoogle Scholar
  13. Kaur D, Bishop GD (2013) Cardiovascular responses to stress in Singapore and India. Int J Psychophysiol 87(2):130–140CrossRefPubMedGoogle Scholar
  14. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531CrossRefPubMedGoogle Scholar
  15. Manichaikul A, Palmas W, Rodriguez CJ, Peralta CA, Divers J, Guo X, Chen WM, Wong Q, Williams K, Kerr KF, Taylor KD, Tsai MY, Goodarzi MO, Sale MM, Diez-Roux AV, Rich SS, Rotter JI, Mychaleckyj JC (2012) Population structure of Hispanics in the United States: the multi-ethnic study of atherosclerosis. PLoS Genet 8(4):e1002640CrossRefPubMedCentralPubMedGoogle Scholar
  16. Murdoch JD, Speed WC, Pakstis AJ, Heffelfinger CE, Kidd KK (2013) Worldwide population variation and haplotype analysis at the serotonin transporter gene SLC6A4 and implications for association studies. Biol Psychiatry 74(12):879–889CrossRefPubMedGoogle Scholar
  17. Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5:32–38CrossRefPubMedGoogle Scholar
  18. Odgerel Z, Talati A, Hamilton SP, Levinson DF, Weissman MM (2013) Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health’s Collaborative Center for Genomic Studies. Transl Psychiatry 3:e307CrossRefPubMedCentralPubMedGoogle Scholar
  19. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. PNAS 90:2542–2546CrossRefPubMedCentralPubMedGoogle Scholar
  20. Reich D, Patterson N, Campbell D, Tandon A, Mazieres S, Ray N, Parra MV et al (2012) Reconstructing Native American population history. Nature 488:370–374CrossRefPubMedCentralPubMedGoogle Scholar
  21. SAS Institute Incorporated (2005) SAS/GENETICS 9.1 User’s Guide. SAS Institute, Cary, NC, USAGoogle Scholar
  22. Thornberry TP, Henry KL (2013) Intergenerational continuity in maltreatment. J Abnorm Child Psychol 41(4):555–569CrossRefPubMedCentralPubMedGoogle Scholar
  23. Vijayendran M, Cutrona C, Beach SRH, Brody GH, Russell D, Phillbert RA (2012) The relationship of the serotonin transporter (SLC6A4) extra long variant to gene expression in an African American sample. Am J Med Genet B Neuropsychiatr Genet 159B:611–612CrossRefPubMedCentralPubMedGoogle Scholar
  24. Wang S, Ray N, Rojas W, Parra MV, Bedoya G, Gallo C, Poletti G et al (2008) Geographic patterns of genome admixture in Latin Americans Mestizos. PLoS Genet 4:e1000037CrossRefPubMedCentralPubMedGoogle Scholar
  25. Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL (2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 11:224–226CrossRefPubMedGoogle Scholar
  26. Wray NR, James MR, Gordon DS, Dumenil T, Ryan L, Coventry WL, Statham DJ, Pergadia ML, Madden PA, Heath AC, Montgomery GW, Martin NG (2009) Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiatry 66:468–476CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Brett C. Haberstick
    • 1
    Email author
  • Andrew Smolen
    • 1
  • Redford B. Williams
    • 2
  • George D. Bishop
    • 3
    • 4
  • Vangie A. Foshee
    • 5
  • Terence P. Thornberry
    • 6
  • Rand Conger
    • 7
  • Ilene C. Siegler
    • 2
  • Xiaodong Zhang
    • 2
    • 8
    • 9
  • Jason D. Boardman
    • 10
  • Zygmunt Frajzyngier
    • 11
  • Michael C. Stallings
    • 1
  • M. Brent Donnellan
    • 12
  • Carolyn T. Halpern
    • 13
  • Kathleen Mullan Harris
    • 14
    • 15
  1. 1.Institute for Behavioral GeneticsUniversity of Colorado BoulderBoulderUSA
  2. 2.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  3. 3.Yale-NUS CollegeSingaporeSingapore
  4. 4.Department of PsychologyNational University of SingaporeSingaporeSingapore
  5. 5.Department of Human Behavior, Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA
  6. 6.Department of Criminology & Criminal JusticeUniversity of MarylandCollege ParkUSA
  7. 7.Department of Human EcologyUniversity of California, DavisDavisUSA
  8. 8.Neuroscience & Behavioral Disorders ProgramDuke-NUS Graduate Medical SchoolSingaporeSingapore
  9. 9.Department of PhysiologyNational University of SingaporeSingaporeSingapore
  10. 10.Institute of Behavioral ScienceUniversity of Colorado BoulderBoulderUSA
  11. 11.Department of LinguisticsUniversity of Colorado BoulderBoulderUSA
  12. 12.Department of PsychologyMichigan State UniversityEast LansingUSA
  13. 13.Department of Maternal and Child Health, Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA
  14. 14.Department of SociologyUniversity of North Carolina at Chapel HillChapel HillUSA
  15. 15.Carolina Population CenterUniversity of North Carolina at Chapel HillChapel HillUSA

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