A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression

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A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression. / Wei, Ya Bin; McCarthy, Michael; Ren, Hongyan; Carrillo-Roa, Tania; Shekhtman, Tatyana; DeModena, Anna; Liu, Jia Jia; Leckband, Susan G; Mors, Ole; Rietschel, Marcella; Henigsberg, Neven; Cattaneo, Annamaria; Binder, Elisabeth B; Aitchison, Katherine J; Kelsoe, John R.

I: Molecular Psychiatry, Bind 25, 2020, s. 1312-1322.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Wei, YB, McCarthy, M, Ren, H, Carrillo-Roa, T, Shekhtman, T, DeModena, A, Liu, JJ, Leckband, SG, Mors, O, Rietschel, M, Henigsberg, N, Cattaneo, A, Binder, EB, Aitchison, KJ & Kelsoe, JR 2020, 'A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression', Molecular Psychiatry, bind 25, s. 1312-1322. https://doi.org/10.1038/s41380-019-0397-1

APA

Wei, Y. B., McCarthy, M., Ren, H., Carrillo-Roa, T., Shekhtman, T., DeModena, A., Liu, J. J., Leckband, S. G., Mors, O., Rietschel, M., Henigsberg, N., Cattaneo, A., Binder, E. B., Aitchison, K. J., & Kelsoe, J. R. (2020). A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression. Molecular Psychiatry, 25, 1312-1322. https://doi.org/10.1038/s41380-019-0397-1

CBE

Wei YB, McCarthy M, Ren H, Carrillo-Roa T, Shekhtman T, DeModena A, Liu JJ, Leckband SG, Mors O, Rietschel M, Henigsberg N, Cattaneo A, Binder EB, Aitchison KJ, Kelsoe JR. 2020. A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression. Molecular Psychiatry. 25:1312-1322. https://doi.org/10.1038/s41380-019-0397-1

MLA

Vancouver

Author

Wei, Ya Bin ; McCarthy, Michael ; Ren, Hongyan ; Carrillo-Roa, Tania ; Shekhtman, Tatyana ; DeModena, Anna ; Liu, Jia Jia ; Leckband, Susan G ; Mors, Ole ; Rietschel, Marcella ; Henigsberg, Neven ; Cattaneo, Annamaria ; Binder, Elisabeth B ; Aitchison, Katherine J ; Kelsoe, John R. / A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression. I: Molecular Psychiatry. 2020 ; Bind 25. s. 1312-1322.

Bibtex

@article{14158bae6b5942f3bacbb3171383890a,
title = "A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression",
abstract = "Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response.",
author = "Wei, {Ya Bin} and Michael McCarthy and Hongyan Ren and Tania Carrillo-Roa and Tatyana Shekhtman and Anna DeModena and Liu, {Jia Jia} and Leckband, {Susan G} and Ole Mors and Marcella Rietschel and Neven Henigsberg and Annamaria Cattaneo and Binder, {Elisabeth B} and Aitchison, {Katherine J} and Kelsoe, {John R}",
year = "2020",
doi = "10.1038/s41380-019-0397-1",
language = "English",
volume = "25",
pages = "1312--1322",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression

AU - Wei, Ya Bin

AU - McCarthy, Michael

AU - Ren, Hongyan

AU - Carrillo-Roa, Tania

AU - Shekhtman, Tatyana

AU - DeModena, Anna

AU - Liu, Jia Jia

AU - Leckband, Susan G

AU - Mors, Ole

AU - Rietschel, Marcella

AU - Henigsberg, Neven

AU - Cattaneo, Annamaria

AU - Binder, Elisabeth B

AU - Aitchison, Katherine J

AU - Kelsoe, John R

PY - 2020

Y1 - 2020

N2 - Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response.

AB - Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response.

U2 - 10.1038/s41380-019-0397-1

DO - 10.1038/s41380-019-0397-1

M3 - Journal article

C2 - 30874608

VL - 25

SP - 1312

EP - 1322

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -