Evidence map›Paper›PMID 18000641›Full record

ArticleJournal of human genetics2007

A genome-wide scan in forty large pedigrees with multiple sclerosis.

Cristen J Willer, David A Dyment, Stacey Cherny, Sreeram V Ramagopalan, Blanca M Herrera, Katie M E Morrison, A Dessa Sadovnick, Neil J Risch, George C Ebers

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of human genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Genetics of Multiple Sclerosis: An Overview and New Directions.Cold Spring Harbor perspectives in medicine · 2018
    Review
  3. Review
  4. Article
  5. Genetic determinants of risk and progression in multiple sclerosis.Clinica chimica acta; international journal of clinical chemistry · 2015
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. The genetic aspects of multiple sclerosis.Annals of Indian Academy of Neurology · 2009
    Article
  13. Article
  14. Review
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

9 authors.

Cristen J WillerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
David A DymentWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Stacey ChernyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Sreeram V RamagopalanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Blanca M HerreraWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Katie M E MorrisonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
A Dessa SadovnickDepartment of Neurology, University of British Columbia, Vancouver, BC, Canada.
Neil J RischDepartment of Genetics, Stanford University, Stanford, CA, USA.
George C EbersWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. george.ebers@clneuro.oxford.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The epidemiology of multiple sclerosis suggests that a complex interaction of genes and environment contribute to susceptibility. To enrich for families with large genetic effects and to potentially reduce genetic heterogeneity, we screened a sample of 18,794 probands and identified forty families with four or more affected individuals. Within these 40 families, HLA DRB1*15 was present in 70% of affected individuals; the transmission disequilibrium test showed a significant excess in transmission of DRB1*15 alleles to affected individuals (47 transmitted, 19 untransmitted, chi (2) = 11.9, p = 0.00057). A 10 cM genome scan was performed and analyzed for linkage under a parametric model with heterogeneity. No excess of significant sharing was observed (HLOD > 3.3) in the parametric multipoint analysis. No region exceeded that for marker GATA8A05 with an HLOD = 1.11. Follow-up genotyping with 17 microsatellites revealed a significant two-point parametric HLOD = 3.99 at marker D4S1597. Transmission disequilibrium tests for markers in this candidate region showed no transmission distortion. A scan for variants in a gene adjacent to D4S1597, PALLD, was negative for synonymous or nonsynonymous changes. A final multipoint scan incorporating all microsatellites in the region provided an HLOD = 1.30. The inability to find significant linkage in these highly penetrant families suggests that linkage is not the optimal tool for dissecting the inheritance of MS.

Indexed as

PedigreeFamily HealthGenetic LinkageGenetic Predisposition to DiseaseGenome, HumanGenomicsHLA-DR AntigensHLA-DRB1 ChainsHumansLinkage DisequilibriumLod ScoreMultiple SclerosisPenetranceHLA-DR AntigensHLA-DRB1 Chains

Identifiers

PMID18000641

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.