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Importance of different types of prior knowledge in selecting genome-wide findings for follow-up.

ABSTRACT: Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts' opinions and empirical evidence to estimate the relative importance of 15 types of information at the single-nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two-round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta-analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta-analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research.

SUBMITTER: Minelli C

PROVIDER: S-EPMC3725558 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Importance of different types of prior knowledge in selecting genome-wide findings for follow-up.

Minelli Cosetta C De Grandi Alessandro A Weichenberger Christian X CX Gögele Martin M Modenese Mirko M Attia John J Barrett Jennifer H JH Boehnke Michael M Borsani Giuseppe G Casari Giorgio G Fox Caroline S CS Freina Thomas T Hicks Andrew A AA Marroni Fabio F Parmigiani Giovanni G Pastore Andrea A Pattaro Cristian C Pfeufer Arne A Ruggeri Fabrizio F Schwienbacher Christine C Taliun Daniel D Pramstaller Peter P PP Domingues Francisco S FS Thompson John R JR

Genetic epidemiology 20130201 2

Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts' opinions and empirical evidence to estimate the relative importance of 15 types of information at the single-nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two-round Delphi survey. Empirical evidence was ob ...[more]

PMID: 23307621

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Project description:ObjectivesTo assess computed tomography (CT) and magnetic resonance imaging (MRI) findings of intramuscular hemangiomas (IMHs) in oral and maxillofacial region and correlate them with the histopathological classifications for selecting optimum management.MethodsThe clinical data and pretreatment findings of 32 patients with pathologically proven IMHs on CT (n = 10), MRI (n = 27), or both (n = 5) were analyzed retrospectively. Correspondence of clinical and imaging characters with 3 different pathological classifications (cavernous, capillary, and mixed) of IMHs was studied. A number of pitfalls and overlap of imaging features can result in misdiagnosis of different IMHs lesions.ResultsFour patients had multi-muscular lesions, and 28 had single-muscular lesions. The predilection site were the tongue (11 cases, 34.4%) and the masseter muscle (10 cases, 31.2%). Cavernous type (17 cases, 53.1%) was the most common IMHs type. All patients showed slightly hypointense or isointense on T1-weighted imaging, 3 patients showed hyperintense on T2-weighted imaging and the others showed slightly hyperintense. The most common enhancement pattern was progressive (29 cases, 90.6%). The capillary type (9 cases, 28.1%) and mixed type (6 cases, 28.1%) of IMHs on imaging indicated characteristics of lesions with rich blood supply status, the cavernous type (17cases, 53.1%) of IMHs belonged to relatively poor blood supply lesions. A total of 5 patients (15.6%) were initially misdiagnosed, there were recurrences in 4 IMHs patients. Extra functional MRI (fMRI) was performed on these 5 misdiagnosed patients, the average ADC of the 5 patients was 1.50 × 10-3 mm2/s. The presence of vermicular vessels was different among these three types of IMHs.ConclusionsThe reason for the misdiagnosis in localized IMHs may be the obvious border of mass-like lesions and the lack of enlarged vessels. Combined evaluation of presence of vermicular vessels and fMRI might be more accurately for determining the IMHs and create a preoperative plan.

Project description:RationalesThe natural history of fibromuscular dysplasia (FMD) is unclear. Furthermore, the correlation between radiologic findings and clinical significance has not been documented. Previously, the development of new vascular symptoms was reported in a small number of patients, but some of these symptoms were from other vascular causes. New arterial lesions were rarely observed during follow-up in the previous reports.Patient concernsA 40-year-old man was admitted due to dysarthria and left-sided weakness. He had developed flank pain due to bilateral renal infarction about 10 months earlier. He had no known risk factors for atherosclerosis. Initial neurological examination revealed a mild weakness and central facial palsy on the left side.DiagnosesDiffusion-weighted magnetic resonance imaging revealed a small acute infarction in the right insular cortex. Magnetic resonance angiography and digital subtraction angiography showed a severe stenosis with post-dilatation in the right internal carotid artery (ICA). There was a focal ectatic lesion in the left ICA. On the previous abdominal computed tomography angiography (CTA), there were arterial lesions suggestive of dissection in the bilateral renal arteries and a rod-shaped ectasia in the left common iliac artery (CIA). The pathological diagnosis was mixed-type FMD involving the intima and media.InterventionsThe patient was prescribed antiplatelet agents for prevention of further ischemic events and followed up regularly.OutcomesSeven years after the initial renal infarction, the patient developed abdominal pain radiating to the back. Abdominal CTA revealed that an aortic dissection had developed in the infrarenal aorta, which was shown as normal previously. The ectasia in the left CIA and left ICA showed no interval changes during follow-up.LessonsWe present a patient who developed spontaneous symptomatic dissection of the bilateral renal arteries, right ICA, and abdominal aorta during 7 years of follow-up, which were caused by pathologically confirmed FMD. Besides the symptomatic multifocal dissection, the patient showed an asymptomatic multifocal ectasia on cerebral and abdominal angiographies that had not changed over 7 years.

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Importance of different types of prior knowledge in selecting genome-wide findings for follow-up.

Publications

Importance of different types of prior knowledge in selecting genome-wide findings for follow-up.

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