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.

Z. Odgerel; A. Talati; S. P. Hamilton; D. F. Levinson; M. M. Weissman

doi:10.1038/tp.2013.80

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.

Z. Odgerel, A. Talati, S. P. Hamilton, D. F. Levinson, M. M. Weissman

Vagelos College of Physicians and Surgeons

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

Abstract

A number of studies have suggested DNA sequence variability in the serotonin transporter gene (SLC6A4) between European-American (EA) and African-American (AA) populations, which could be clinically important, given the central role SLC6A4 has in serotonin transmission. However, these studies have had relatively small samples, used self-reported measures of race, and have only tested the promoter-linked polymorphism 5-HTTLPR. Here we genotype 5-HTTLPR and rs25531, a neighboring functional polymorphism, in 954 AA and 2622EA subjects from a National Institute of Mental Health repository sample. Genotyping was performed using fragment analysis by capillary electrophoresis. AA, as compared with EA, groups had lower frequencies of the S allele (0.25 vs 0.43) and SS genotype (0.06 vs 0.19) at 5-HTTLPR, and higher rates of the G allele at rs25531 (0.21 vs 0.075). A rare xL variant at 5-HTTLPR was also more common among AAs (0.017 vs 0.008). When the polymorphisms were redefined into a high- and low-transcription haplotypes, the AA group showed significantly fewer low-transcription variants (χ(2)=4.8, P=0.03). No genotypes were associated with major depression, any anxiety disorder, or neuroticism in either EA or AA populations. This is the largest study to show SLC6A4 genotype differences between EA and AA populations, and the first to include rs25531. Lack of associations with clinical outcomes may reflect untested moderating environmental influences.

Original language	English
Pages (from-to)	e307
Journal	Translational Psychiatry
Volume	3
DOIs	https://doi.org/10.1038/tp.2013.80
Publication status	Published - 2013

Bibliographical note

Funding Information:
In the past two years, Dr Weissman received funding from the NIMH, NIDA, NARSAD, the Sackler Foundation, the Templeton Foundation and the Interstitial Cystitis Association, and received royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press and MultiHealth Systems. None of these present a conflict of interest with this manuscript. The remaining authors declare no conflict of interest.

Funding Information:
Access to the sample was provided as part of an NIMH program project P01MH60970 (Weissman, PI). The present study is supported by NIMH Conte Center 1P50MH090966 (Jay Gingrich, MD, PhD, PI) and 1RC2MH089916 (M Weissman, PI). Dr Talati is funded by K01DA029598. Biomaterials and phenotypic data were obtained from the following projects that participated in the NIMH Control Samples: Control subjects from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH-GI), data and biomaterials are being collected by the ’Molecular Genetics of Schizophrenia II’ (MGS-2) collaboration. The investigators and coinvestigators are ENH/Northwestern University, Evanston, IL, MH059571, Pablo V. Gejman, MD (Collaboration Coordinator; PI), Alan R. Sanders, MD; Emory University School of Medicine, Atlanta, GA,MH59587, Farooq Amin, MD (PI); Columbia University, M Jay A Gingrich, MD (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Bueaola, APRN, BC, MSN. (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879, C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA,MH59566, Raymond Crowe, MD (PI), Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert Freedman, MD (PI); Stanford University, Stanford, CA, MH061675 and MH089916, Douglas Levinson MD (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School of Medicine, New York, NY,MH59586, Jeremy Silverman, PhD (PI). The samples were collected by Vishwajit Nimgaonkar’s group at the University of Pittsburgh, as part of a multi-institutional collaborative research project with Jordan Smoller, MD, DSc., and Pamela Sklar, MD, PhD, Massachusetts General Hospital (grant MH 63420). Data and biomaterials used in Study 23 were collected by the University of Pittsburgh and funded by an NIMH grant (Genetic Susceptibility in Schizophrenia, MH 56242) to Vishwajit Nimgaonkar, MD, PhD Additional Principal Investigators on this grant include Smita Deshpande, MD, Dr Ram Moanohar Lohia Hospital, New Delhi, India; and Michael Owen, MD, PhD, University of Wales College of Medicine, Cardiff, UK.

Funding

In the past two years, Dr Weissman received funding from the NIMH, NIDA, NARSAD, the Sackler Foundation, the Templeton Foundation and the Interstitial Cystitis Association, and received royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press and MultiHealth Systems. None of these present a conflict of interest with this manuscript. The remaining authors declare no conflict of interest. Access to the sample was provided as part of an NIMH program project P01MH60970 (Weissman, PI). The present study is supported by NIMH Conte Center 1P50MH090966 (Jay Gingrich, MD, PhD, PI) and 1RC2MH089916 (M Weissman, PI). Dr Talati is funded by K01DA029598. Biomaterials and phenotypic data were obtained from the following projects that participated in the NIMH Control Samples: Control subjects from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH-GI), data and biomaterials are being collected by the ’Molecular Genetics of Schizophrenia II’ (MGS-2) collaboration. The investigators and coinvestigators are ENH/Northwestern University, Evanston, IL, MH059571, Pablo V. Gejman, MD (Collaboration Coordinator; PI), Alan R. Sanders, MD; Emory University School of Medicine, Atlanta, GA,MH59587, Farooq Amin, MD (PI); Columbia University, M Jay A Gingrich, MD (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Bueaola, APRN, BC, MSN. (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879, C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA,MH59566, Raymond Crowe, MD (PI), Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert Freedman, MD (PI); Stanford University, Stanford, CA, MH061675 and MH089916, Douglas Levinson MD (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School of Medicine, New York, NY,MH59586, Jeremy Silverman, PhD (PI). The samples were collected by Vishwajit Nimgaonkar’s group at the University of Pittsburgh, as part of a multi-institutional collaborative research project with Jordan Smoller, MD, DSc., and Pamela Sklar, MD, PhD, Massachusetts General Hospital (grant MH 63420). Data and biomaterials used in Study 23 were collected by the University of Pittsburgh and funded by an NIMH grant (Genetic Susceptibility in Schizophrenia, MH 56242) to Vishwajit Nimgaonkar, MD, PhD Additional Principal Investigators on this grant include Smita Deshpande, MD, Dr Ram Moanohar Lohia Hospital, New Delhi, India; and Michael Owen, MD, PhD, University of Wales College of Medicine, Cardiff, UK.

Funders	Funder number
National Institute of Mental Health	K01DA029598, 1RC2MH089916, R01MH063420, 1P50MH090966
John Templeton Foundation
Interstitial Cystitis Association
National Alliance for Research on Schizophrenia and Depression
Raymond and Beverly Sackler Foundation
National Institute of Development Administration

ASJC Scopus Subject Areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/tp.2013.80

Cite this

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. / Odgerel, Z.; Talati, A.; Hamilton, S. P. et al.
In: Translational Psychiatry, Vol. 3, 2013, p. e307.

Research output: Contribution to journal › Article › peer-review

@article{fbb2d7749c424e1a9e5a4db123bb3696,

title = "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.",

abstract = "A number of studies have suggested DNA sequence variability in the serotonin transporter gene (SLC6A4) between European-American (EA) and African-American (AA) populations, which could be clinically important, given the central role SLC6A4 has in serotonin transmission. However, these studies have had relatively small samples, used self-reported measures of race, and have only tested the promoter-linked polymorphism 5-HTTLPR. Here we genotype 5-HTTLPR and rs25531, a neighboring functional polymorphism, in 954 AA and 2622EA subjects from a National Institute of Mental Health repository sample. Genotyping was performed using fragment analysis by capillary electrophoresis. AA, as compared with EA, groups had lower frequencies of the S allele (0.25 vs 0.43) and SS genotype (0.06 vs 0.19) at 5-HTTLPR, and higher rates of the G allele at rs25531 (0.21 vs 0.075). A rare xL variant at 5-HTTLPR was also more common among AAs (0.017 vs 0.008). When the polymorphisms were redefined into a high- and low-transcription haplotypes, the AA group showed significantly fewer low-transcription variants (χ(2)=4.8, P=0.03). No genotypes were associated with major depression, any anxiety disorder, or neuroticism in either EA or AA populations. This is the largest study to show SLC6A4 genotype differences between EA and AA populations, and the first to include rs25531. Lack of associations with clinical outcomes may reflect untested moderating environmental influences.",

author = "Z. Odgerel and A. Talati and Hamilton, {S. P.} and Levinson, {D. F.} and Weissman, {M. M.}",

note = "Funding Information: In the past two years, Dr Weissman received funding from the NIMH, NIDA, NARSAD, the Sackler Foundation, the Templeton Foundation and the Interstitial Cystitis Association, and received royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press and MultiHealth Systems. None of these present a conflict of interest with this manuscript. The remaining authors declare no conflict of interest. Funding Information: Access to the sample was provided as part of an NIMH program project P01MH60970 (Weissman, PI). The present study is supported by NIMH Conte Center 1P50MH090966 (Jay Gingrich, MD, PhD, PI) and 1RC2MH089916 (M Weissman, PI). Dr Talati is funded by K01DA029598. Biomaterials and phenotypic data were obtained from the following projects that participated in the NIMH Control Samples: Control subjects from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH-GI), data and biomaterials are being collected by the {\textquoteright}Molecular Genetics of Schizophrenia II{\textquoteright} (MGS-2) collaboration. The investigators and coinvestigators are ENH/Northwestern University, Evanston, IL, MH059571, Pablo V. Gejman, MD (Collaboration Coordinator; PI), Alan R. Sanders, MD; Emory University School of Medicine, Atlanta, GA,MH59587, Farooq Amin, MD (PI); Columbia University, M Jay A Gingrich, MD (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Bueaola, APRN, BC, MSN. (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879, C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA,MH59566, Raymond Crowe, MD (PI), Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert Freedman, MD (PI); Stanford University, Stanford, CA, MH061675 and MH089916, Douglas Levinson MD (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School of Medicine, New York, NY,MH59586, Jeremy Silverman, PhD (PI). The samples were collected by Vishwajit Nimgaonkar{\textquoteright}s group at the University of Pittsburgh, as part of a multi-institutional collaborative research project with Jordan Smoller, MD, DSc., and Pamela Sklar, MD, PhD, Massachusetts General Hospital (grant MH 63420). Data and biomaterials used in Study 23 were collected by the University of Pittsburgh and funded by an NIMH grant (Genetic Susceptibility in Schizophrenia, MH 56242) to Vishwajit Nimgaonkar, MD, PhD Additional Principal Investigators on this grant include Smita Deshpande, MD, Dr Ram Moanohar Lohia Hospital, New Delhi, India; and Michael Owen, MD, PhD, University of Wales College of Medicine, Cardiff, UK.",

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TY - JOUR

T1 - 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.

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AU - Talati, A.

AU - Hamilton, S. P.

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PY - 2013

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N2 - A number of studies have suggested DNA sequence variability in the serotonin transporter gene (SLC6A4) between European-American (EA) and African-American (AA) populations, which could be clinically important, given the central role SLC6A4 has in serotonin transmission. However, these studies have had relatively small samples, used self-reported measures of race, and have only tested the promoter-linked polymorphism 5-HTTLPR. Here we genotype 5-HTTLPR and rs25531, a neighboring functional polymorphism, in 954 AA and 2622EA subjects from a National Institute of Mental Health repository sample. Genotyping was performed using fragment analysis by capillary electrophoresis. AA, as compared with EA, groups had lower frequencies of the S allele (0.25 vs 0.43) and SS genotype (0.06 vs 0.19) at 5-HTTLPR, and higher rates of the G allele at rs25531 (0.21 vs 0.075). A rare xL variant at 5-HTTLPR was also more common among AAs (0.017 vs 0.008). When the polymorphisms were redefined into a high- and low-transcription haplotypes, the AA group showed significantly fewer low-transcription variants (χ(2)=4.8, P=0.03). No genotypes were associated with major depression, any anxiety disorder, or neuroticism in either EA or AA populations. This is the largest study to show SLC6A4 genotype differences between EA and AA populations, and the first to include rs25531. Lack of associations with clinical outcomes may reflect untested moderating environmental influences.

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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.

Abstract

Bibliographical note

Funding

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UN SDGs

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