Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes

T.G. Richardson, C.C. Minica, J. Heron, J. Tavare, A. MacKenzie, I. Day, G. Lewis, M. Hickman, J.M. Vink, J. Gelernter, H.R. Kranzler, L.A. Farrer, M. Munafò, D. Wynick

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

There is a large body of pre-clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In-vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele was 40% less active than the GG allele in driving galanin expression. Our hypothesis was to investigate the effect of this galanin enhancer genotype on a range of variables that relate to the known functions of the galaninergic system in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of young adults (N=169-6,078). Initial findings showed a positive relationship of cannabis usage (OR=2.070, P=0.007, N=406 (individuals who had used cannabis at least once within the last 12 months, total sample size 2731) with the GG haplotype, consistent with the previous published data linking galanin with an increased release of dopamine. As our sample size was relatively small we replicated the analysis in a larger cohort of 2,224 African Americans and 1,840 European Americans, but no discernible trend across genotypes was observed for the relationship with cannabis usage. Further, we found no association of the galanin enhancer genotype with any of the other pathophysiological parameters measured. These findings emphasise that preclinical data does not always predict clinical outcomes in cohort studies, noting that association studies are subject to multiple confounders.
Original languageEnglish
Pages (from-to)654-664
Number of pages11
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume165
Issue number8
DOIs
Publication statusPublished - 2014

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Galanin
Genotype
Phenotype
Cannabis
Sample Size
Alleles
Neuropeptides
African Americans
Haplotypes
Transfection
Longitudinal Studies
Young Adult
Dopamine
Cohort Studies
Parents
Depression
Neurons

Cite this

Richardson, T.G. ; Minica, C.C. ; Heron, J. ; Tavare, J. ; MacKenzie, A. ; Day, I. ; Lewis, G. ; Hickman, M. ; Vink, J.M. ; Gelernter, J. ; Kranzler, H.R. ; Farrer, L.A. ; Munafò, M. ; Wynick, D. / Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes. In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2014 ; Vol. 165, No. 8. pp. 654-664.
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abstract = "There is a large body of pre-clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In-vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele was 40{\%} less active than the GG allele in driving galanin expression. Our hypothesis was to investigate the effect of this galanin enhancer genotype on a range of variables that relate to the known functions of the galaninergic system in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of young adults (N=169-6,078). Initial findings showed a positive relationship of cannabis usage (OR=2.070, P=0.007, N=406 (individuals who had used cannabis at least once within the last 12 months, total sample size 2731) with the GG haplotype, consistent with the previous published data linking galanin with an increased release of dopamine. As our sample size was relatively small we replicated the analysis in a larger cohort of 2,224 African Americans and 1,840 European Americans, but no discernible trend across genotypes was observed for the relationship with cannabis usage. Further, we found no association of the galanin enhancer genotype with any of the other pathophysiological parameters measured. These findings emphasise that preclinical data does not always predict clinical outcomes in cohort studies, noting that association studies are subject to multiple confounders.",
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Richardson, TG, Minica, CC, Heron, J, Tavare, J, MacKenzie, A, Day, I, Lewis, G, Hickman, M, Vink, JM, Gelernter, J, Kranzler, HR, Farrer, LA, Munafò, M & Wynick, D 2014, 'Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes' American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, vol. 165, no. 8, pp. 654-664. https://doi.org/10.1002/ajmg.b.32270

Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes. / Richardson, T.G.; Minica, C.C.; Heron, J.; Tavare, J.; MacKenzie, A.; Day, I.; Lewis, G.; Hickman, M.; Vink, J.M.; Gelernter, J.; Kranzler, H.R.; Farrer, L.A.; Munafò, M.; Wynick, D.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 165, No. 8, 2014, p. 654-664.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes

AU - Richardson, T.G.

AU - Minica, C.C.

AU - Heron, J.

AU - Tavare, J.

AU - MacKenzie, A.

AU - Day, I.

AU - Lewis, G.

AU - Hickman, M.

AU - Vink, J.M.

AU - Gelernter, J.

AU - Kranzler, H.R.

AU - Farrer, L.A.

AU - Munafò, M.

AU - Wynick, D.

PY - 2014

Y1 - 2014

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AB - There is a large body of pre-clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In-vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele was 40% less active than the GG allele in driving galanin expression. Our hypothesis was to investigate the effect of this galanin enhancer genotype on a range of variables that relate to the known functions of the galaninergic system in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of young adults (N=169-6,078). Initial findings showed a positive relationship of cannabis usage (OR=2.070, P=0.007, N=406 (individuals who had used cannabis at least once within the last 12 months, total sample size 2731) with the GG haplotype, consistent with the previous published data linking galanin with an increased release of dopamine. As our sample size was relatively small we replicated the analysis in a larger cohort of 2,224 African Americans and 1,840 European Americans, but no discernible trend across genotypes was observed for the relationship with cannabis usage. Further, we found no association of the galanin enhancer genotype with any of the other pathophysiological parameters measured. These findings emphasise that preclinical data does not always predict clinical outcomes in cohort studies, noting that association studies are subject to multiple confounders.

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DO - 10.1002/ajmg.b.32270

M3 - Article

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EP - 664

JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

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