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Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs

Molecular Psychiatry volume 5, pages 216–219 (2000)Cite this article

Abstract

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P = 0.03), including the subscale of shyness (P = 0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits.

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References

  1. Ohara K, Nagai M, Suzuki Y, Ochiai M, Ohara K . Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene Psychiatry Res 1998; 81: 277–279

    Article  CAS  Google Scholar 

  2. Ishiguro H, Arinami T, Yamada K, Otsuka Y, Toru M, Shibuya H . An association study between a transcriptional polymorphism in the serotonin transporter gene and panic disorder in a Japanese population Psychiatry Clin Neurosci 1997; 51: 333–335

    Article  CAS  Google Scholar 

  3. Deckert J, Catalano M, Heils A, Di Bella D, Friess F, Politi E et al. Functional promoter polymorphism of the human serotonin transporter: lack of association with panic disorder Psychiatr Genet 1997; 7: 45–47

    Article  CAS  Google Scholar 

  4. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 1996; 274: 1527–1531

    Article  CAS  Google Scholar 

  5. Costa PTJ, McCrae RR . Revised NEO Personality Inventory (NEO-PI-R) and NEO Five Inventory (NEO-FFI) Professional Manual Psychological Assessment Resources: Florida 1992

    Google Scholar 

  6. Cloninger CR, Przybeck T, Svrakic D . The Temperament and Character Inventory: A Guide to its Development and Use. Center for Psychobiology of Personality, Washington University: St Louis 1994 pp–1–184

  7. Ricketts MH, Hamer RM, Sage JI, Manowitz P, Feng F, Menza MA . Association of a serotonin transporter gene promoter polymorphism with harm avoidance behaviour in an elderly population Psychiatr Genet 1998; 8: 41–44

    Article  CAS  Google Scholar 

  8. Katsuragi S, Kunugi H, Sano A, Tsutsumi T, Isogawa K, Nanko S et al. Association between the serotonin transporter gene polymorphism and anxiety-related traits Biol Psychiatry 1999; 45: 368–370

    Article  CAS  Google Scholar 

  9. Murakami F, Shimomura T, Kotani K, Ikawa S, Nanba E, Adachi K . Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese J Hum Gen 1999; 44: 15–17

    Article  CAS  Google Scholar 

  10. Mazzanti CM, Lappalainen J, Long JC, Bengel D, Naukkarinen H, Eggert M et al. Role of the serotonin transporter promoter polymorphism in anxiety-related traits Arch Gen Psychiatry 1998; 55: 936–940

    Article  CAS  Google Scholar 

  11. Ebstein RP, Gritsenko I, Nemanov L, Frisch A, Osher Y, Belmaker RH . No association between the serotonin transporter gene regulatory region polymorphism and the tridimensional personality questionnaire (TPQ) temperament of harm avoidance Mol Psychiatry 1997; 2: 224–226

    Article  CAS  Google Scholar 

  12. Gelernter J, Kranzler H, Coccaro EF, Siever LJ, New AS . Serotonin transporter protein gene polymorphism and personality measures in African American and European American subjects Am J Psychiatry 1998; 155: 1332–1338

    Article  CAS  Google Scholar 

  13. Jorm AF, Henderson AS, Jacomb PA, Christensen H, Korten AE, Rodgers B et al. An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms Mol Psychiatry 1998; 3: 449–451

    Article  CAS  Google Scholar 

  14. Flory JD, Manuck SB, Ferrell RE, Dent KM, Peters DG, Muldoom MF . Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism Mol Psychiatry 1999; 4: 93–96

    Article  CAS  Google Scholar 

  15. Ball D, Hill L, Freeman B, Eley TC, Strelau J, Riemann R et al. The serotonin transporter gene and peer-rated neuroticism Neuroreport 1997; 8: 1301–1304

    Article  CAS  Google Scholar 

  16. Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL . Genetic variation in the serotonin transporter promotion region affects serotonin uptake in human blood platelets Am J Med Genet 1999; 88: 83–87

    Article  CAS  Google Scholar 

  17. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC . Quantitative trait locus for reading-disability on chromosome-6 Science 1994; 266: 276–279

    Article  CAS  Google Scholar 

  18. Benjamin J, Osher Y, Kotler M, Gritsenko I, Nemanov L, Belmaker RH et al. Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT) Mol Psychiatry 2000; 5: 96–100

    Article  CAS  Google Scholar 

  19. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking Nat Genet 1996; 12: 78–80

    Article  CAS  Google Scholar 

  20. Schwimmer M, Montag I . Sensation seeking and the five-factor model Man and Work 1996; 7: 22–45. In Hebrew; English abstract 70–71

    Google Scholar 

  21. McCrae R, Costa P . Personality trait structure as a human universal American Psychologist 1997; 52: 509–516

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by grant No. 95–98 of the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel (JB and DH).

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Authors and Affiliations

  1. Beer Sheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, POB 4600, Beer Sheva, Israel

    Y Osher

  2. Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    D Hamer

  3. Department of Psychiatry, Soroka Medical Center, Ben Gurion University of the Negev, POB 151, Beer Sheva, Israel

    J Benjamin

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  1. Y Osher
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  3. J Benjamin
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Correspondence to J Benjamin.

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Osher, Y., Hamer, D. & Benjamin, J. Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs. Mol Psychiatry 5, 216–219 (2000). https://doi.org/10.1038/sj.mp.4000660

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  • DOI: https://doi.org/10.1038/sj.mp.4000660

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