Evidence map›Paper›PMID 34972135›Full record

ArticlePloS one2021

A replication study separates polymorphisms behind migraine with and without depression.

Peter Petschner, Daniel Baksa, Gabor Hullam, Dora Torok, Andras Millinghoffer, J F William Deakin, Gyorgy Bagdy, Gabriella Juhasz

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The interictal transcriptomic map of migraine without aura.The journal of headache and pain · 2025
    Article
  4. Review
  5. Review
  6. 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

8 authors at 3 institutions in 3 countries.

Peter PetschnerBioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, Japan.
Daniel BaksaDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-7826-9179
Gabor HullamDepartment of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary.
Dora TorokDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
Andras MillinghofferMTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
J F William DeakinNeuroscience and Psychiatry Unit, Division of Neuroscience and Experimental Psychology, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Gyorgy BagdyDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
Gabriella JuhaszDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-5975-4267
Semmelweis University · HUBudapest University of Technology and Economics · HUManchester Academic Health Science Centre · GB

Funding

Department of Health
6 · The paper itself

Abstract

The largest migraine genome-wide association study identified 38 candidate loci. In this study we assessed whether these results replicate on a gene level in our European cohort and whether effects are altered by lifetime depression. We tested SNPs of the loci and their vicinity with or without interaction with depression in regression models. Advanced analysis methods such as Bayesian relevance analysis and a neural network based classifier were used to confirm findings. Main effects were found for rs2455107 of PRDM16 (OR = 1.304, p = 0.007) and five intergenic polymorphisms in 1p31.1 region: two of them showed risk effect (OR = 1.277, p = 0.003 for both rs11209657 and rs6686879), while the other three variants were protective factors (OR = 0.4956, p = 0.006 for both rs12090642 and rs72948266; OR = 0.4756, p = 0.005 for rs77864828). Additionally, 26 polymorphisms within ADGRL2, 2 in REST, 1 in HPSE2 and 33 mostly intergenic SNPs from 1p31.1 showed interaction effects. Among clumped results representing these significant regions, only rs11163394 of ADGRL2 showed a protective effect (OR = 0.607, p = 0.002), all other variants were risk factors (rs1043215 of REST with the strongest effect: OR = 6.596, p = 0.003). Bayesian relevance analysis confirmed the relevance of intergenic rs6660757 and rs12128399 (p31.1), rs1043215 (REST), rs1889974 (HPSE2) and rs11163394 (ADGRL2) from depression interaction results, and the moderate relevance of rs77864828 and rs2455107 of PRDM16 from main effect analysis. Both main and interaction effect SNPs could enhance predictive power with the neural network based classifier. In summary, we replicated p31.1, PRDM16, REST, HPSE2 and ADGRL2 genes with classic genetic and advanced analysis methods. While the p31.1 region and PRDM16 are worthy of further investigations in migraine in general, REST, HPSE2 and ADGRL2 may be prime candidates behind migraine pathophysiology in patients with comorbid depression.

Indexed as

Genome-Wide Association StudyPolymorphism, Single NucleotideAdolescentAdultAlgorithmsAllelesBayes TheoremDepressive DisorderDNA-Binding ProteinsEuropeFemaleGenetic Predisposition to DiseaseGenotypeGlucuronidaseHeparanaseHumansADGRL2 protein, humanDNA-Binding ProteinsGlucuronidaseHeparanasePRDM16 protein, humanReceptors, G-Protein-CoupledTranscription Factors

Identifiers

PMID34972135
PMCPMC8719675
OpenAlexW4206794122

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.