Evidence map›Paper›PMID 21716262›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2011

Differential activity by polymorphic variants of a remote enhancer that supports galanin expression in the hypothalamus and amygdala: implications for obesity, depression and alcoholism.

Scott Davidson, Marissa Lear, Lynne Shanley, Benjamin Hing, Amanda Baizan-Edge, Annika Herwig, John P Quinn, Gerome Breen, Peter McGuffin, Andrew Starkey and 2 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
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  12. Non-coding genetic variation shaping mental health.Current opinion in psychology · 2019
    Review
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  16. Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Review
  17. Applications of CRISPR/Cas9 in the Mammalian Central Nervous System.The Yale journal of biology and medicine · 2017
    Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Scott DavidsonSchool of Medical Sciences, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
Marissa Lear
Lynne Shanley
Benjamin Hing
Amanda Baizan-Edge
Annika Herwig
John P Quinn
Gerome Breen
Peter McGuffin
Andrew Starkey
Perry Barrett
Alasdair MacKenzie
University of Aberdeen · GBKing's College London · GBUniversity of Liverpool · GB

Funding

Biotechnology and Biological Sciences Research Council BB/D004659/1Biotechnology and Biological Sciences Research Council BB/D524932/1Biotechnology and Biological Sciences Research Council (BBS/S/2005/12001Medical Research Council G0701003Medical Research Council G0701003(82686)Wellcome Trust 080980Wellcome Trust 080980/Z/06/Z
6 · The paper itself

Abstract

The expression of the galanin gene (GAL) in the paraventricular nucleus (PVN) and in the amygdala of higher vertebrates suggests the requirement for highly conserved, but unidentified, regulatory sequences that are critical to allow the galanin gene to control alcohol and fat intake and modulate mood. We used comparative genomics to identify a highly conserved sequence that lay 42 kb 5' of the human GAL transcriptional start site that we called GAL5.1. GAL5.1 activated promoter activity in neurones of the PVN, arcuate nucleus and amygdala that also expressed the galanin peptide. Analysis in neuroblastoma cells demonstrated that GAL5.1 acted as an enhancer of promoter activity after PKC activation. GAL5.1 contained two polymorphisms; rs2513280(C/G) and rs2513281(A/G), that occurred in two allelic combinations (GG or CA) where the dominant GG alelle occurred in 70-83 % of the human population. Intriguingly, both SNPs were found to be in LD (R(2) of 0.687) with another SNP (rs2156464) previously associated with major depressive disorder (MDD). Recreation of these alleles in reporter constructs and subsequent magnetofection into primary rat hypothalamic neurones showed that the CA allele was 40 % less active than the GG allele. This is consistent with the hypothesis that the weaker allele may affect food and alcohol preference. The linkage of the SNPs analysed in this study with a SNP previously associated with MDD together with the functioning of GAL5.1 as a PVN and amygdala specific enhancer represent a significant advance in our ability to understand alcoholism, obesity and major depressive disorder.

Indexed as

AlcoholismAmygdalaAnimalsBase SequenceCell Line, TumorCells, CulturedDepressionEnhancer Elements, GeneticGalaninGene Expression RegulationGenetic VariationHumansHypothalamusMiceMice, Inbred C57BLMice, Inbred CBAGalanin

Identifiers

PMID21716262
PMCPMC3176579
OpenAlexW2046181038

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.