Evidence map›Paper›PMID 26136518›Full record

ArticleNeurology2015

Mitochondrial DNA sequence variation in multiple sclerosis.

Gregory J Tranah, Adam Santaniello, Stacy J Caillier, Sandra D'Alfonso, Filippo Martinelli Boneschi, Stephen L Hauser, Jorge R Oksenberg

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 3 pooled it
4.9field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. CD4Scientific reports · 2024
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  13. Article
  14. Review
  15. Stem Cell Therapies for Progressive Multiple Sclerosis.Frontiers in cell and developmental biology · 2021
    Review
  16. Article
  17. Intimate Relations-Mitochondria and Ageing.International journal of molecular sciences · 2020
    Review
  18. Review
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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

7 authors at 2 institutions in 1 country.

Gregory J TranahFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy. gtranah@sfcc-cpmc.edu.
Adam SantanielloFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
Stacy J CaillierFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
Sandra D'AlfonsoFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
Filippo Martinelli BoneschiFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
Stephen L HauserFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
Jorge R OksenbergFrom the California Pacific Medical Center Research Institute (G.J.T.), San Francisco, CA; Department of Neurology (A.S., S.J.C., S.L.H., J.R.O.), University of California, San Francisco; Department of Health Sciences (S.D.), UPO and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Avogadro, Novara, Italy; and Department of Neuro-rehabilitation and INSPE (Institute of Experimental Neurology) (F.M.B.), Scientific Institute San Raffaele, Milan, Italy.
University of California, San Francisco · USCalifornia Pacific Medical Center · US

Funding

A Haplotype Map for Multiple SclerosisR01NS049477 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L · 2005 to 2014
$15.3M
GENE LINKAGE STUDY OF MULTIPLE SCLEROSIS SIBLING PAIRSR01NS026799 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L, OKSENBERG, JORGE R. · 1989 to 2018
$6.8M
NINDS Research Education Programs for Residents and Fellows in Neurology, Neurosurgery, Neuropathology, Neuroradiology and Emergency Medicine (R25)R25NS070680 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOSEPHSON, SCOTT ANDREW · 2010 to 2023
$6.8M
Mitochondrial DNA Variation in Human Energy Expenditure and Metabolic RateR03AG032498 · NIA · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI TRANAH, GREGORY J. · 2009 to 2010
$121k
NIA NIH HHS R03AG032498NINDS NIH HHS R01 NS026799NINDS NIH HHS R01NS26799NINDS NIH HHS R01NS4947703NINDS NIH HHS R25 NS070680
6 · The paper itself

Abstract

objectiveTo assess the influence of common mitochondrial DNA (mtDNA) sequence variation on multiple sclerosis (MS) risk in cases and controls part of an international consortium.

methodsWe analyzed 115 high-quality mtDNA variants and common haplogroups from a previously published genome-wide association study among 7,391 cases from the International Multiple Sclerosis Genetics Consortium and 14,568 controls from the Wellcome Trust Case Control Consortium 2 project from 7 countries. Significant single nucleotide polymorphism and haplogroup associations were replicated in 3,720 cases and 879 controls from the University of California, San Francisco.

resultsAn elevated risk of MS was detected among haplogroup JT carriers from 7 pooled clinic sites (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.07-1.24, p = 0.0002) included in the discovery study. The increased risk of MS was observed for both haplogroup T (OR = 1.17, 95% CI = 1.06-1.29, p = 0.002) and haplogroup J carriers (OR = 1.11, 95% CI = 1.01-1.22, p = 0.03). These haplogroup associations with MS were not replicated in the independent sample set. An elevated risk of primary progressive (PP) MS was detected for haplogroup J participants from 3 European discovery populations (OR = 1.49, 95% CI = 1.10-2.01, p = 0.009). This elevated risk was borderline significant in the US replication population (OR = 1.43, 95% CI = 0.99-2.08, p = 0.058) and remained significant in pooled analysis of discovery and replication studies (OR = 1.43, 95% CI = 1.14-1.81, p = 0.002). No common individual mtDNA variants were associated with MS risk.

conclusionsIdentification and validation of mitochondrial genetic variants associated with MS and PPMS may lead to new targets for treatment and diagnostic tests for identifying potential responders to interventions that target mitochondria.

Indexed as

Case-Control StudiesDNA, MitochondrialGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHaplotypesHumansMultiple SclerosisPolymorphism, Single NucleotideWhite PeopleDNA, Mitochondrial

Identifiers

PMID26136518
PMCPMC4520811
OpenAlexW1718676046

What OpenQuestion holds

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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.