Evidence map›Paper›PMID 22353194›Full record

ArticleBMC medical genomics2012

Identification of genetic risk variants for deep vein thrombosis by multiplexed next-generation sequencing of 186 hemostatic/pro-inflammatory genes.

Luca A Lotta, Mark Wang, Jin Yu, Ida Martinelli, Fuli Yu, Serena M Passamonti, Dario Consonni, Emanuela Pappalardo, Marzia Menegatti, Steven E Scherer and 8 more

Abstract read
In one paragraph

Article in BMC medical genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–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

16 citing papers in PubMed.

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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

18 authors.

Luca A LottaAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, U.O.S. Dipartimentale per la Diagnosi e la Terapia delle Coagulopatie, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Mark Wang
Jin Yu
Ida Martinelli
Fuli Yu
Serena M Passamonti
Dario Consonni
Emanuela Pappalardo
Marzia Menegatti
Steven E Scherer
Lora L Lewis
Humeira Akbar
Yuanqing Wu
Matthew N Bainbridge
Donna M Muzny
Pier M Mannucci
Richard A Gibbs
Flora Peyvandi

Funding

The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
NHGRI NIH HHS U54 HG003273
6 · The paper itself

Abstract

backgroundNext-generation DNA sequencing is opening new avenues for genetic association studies in common diseases that, like deep vein thrombosis (DVT), have a strong genetic predisposition still largely unexplained by currently identified risk variants. In order to develop sequencing and analytical pipelines for the application of next-generation sequencing to complex diseases, we conducted a pilot study sequencing the coding area of 186 hemostatic/proinflammatory genes in 10 Italian cases of idiopathic DVT and 12 healthy controls.

resultsA molecular-barcoding strategy was used to multiplex DNA target capture and sequencing, while retaining individual sequence information. Genomic libraries with barcode sequence-tags were pooled (in pools of 8 or 16 samples) and enriched for target DNA sequences. Sequencing was performed on ABI SOLiD-4 platforms. We produced > 12 gigabases of raw sequence data to sequence at high coverage (average: 42X) the 700-kilobase target area in 22 individuals. A total of 1876 high-quality genetic variants were identified (1778 single nucleotide substitutions and 98 insertions/deletions). Annotation on databases of genetic variation and human disease mutations revealed several novel, potentially deleterious mutations. We tested 576 common variants in a case-control association analysis, carrying the top-5 associations over to replication in up to 719 DVT cases and 719 controls. We also conducted an analysis of the burden of nonsynonymous variants in coagulation factor and anticoagulant genes. We found an excess of rare missense mutations in anticoagulant genes in DVT cases compared to controls and an association for a missense polymorphism of FGA (rs6050; p = 1.9 × 10(-5), OR 1.45; 95% CI, 1.22-1.72; after replication in > 1400 individuals).

conclusionsWe implemented a barcode-based strategy to efficiently multiplex sequencing of hundreds of candidate genes in several individuals. In the relatively small dataset of our pilot study we were able to identify bona fide associations with DVT. Our study illustrates the potential of next-generation sequencing for the discovery of genetic variation predisposing to complex diseases.

Indexed as

AdultCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenetic VariationGenomicsHemostasisHigh-Throughput Nucleotide SequencingHumansInflammationMalePilot ProjectsSequence Analysis, DNAVenous Thrombosis

Identifiers

PMID22353194
PMCPMC3305575

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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.