For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
28
views
26
references
 Top references
cited by
71
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      371
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Translational genomics and precision medicine: Moving from the lab to the clinic

      Author(s): , , ,
      Publication date Created:
      Publication date (Electronic):
      Journal: Science
      Publisher: American Association for the Advancement of Science (AAAS)

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Translational genomics aims to improve human health by building on discoveries made through genetics research and applying them in the clinical setting. This progress has been made possible by technological advances in genomics and analytics and by the digital revolution. Such advances should enable the development of prognostic markers, tailored interventions, and the design of prophylactic preventive approaches. We are at the cusp of predicting disease risk for some disorders by means of polygenic risk scores integrated with classical epidemiological risk factors. This should lead to better risk stratification and clinical decision-making. A deeper understanding of the link between genome-wide sequence and association with well-characterized phenotypes will empower the development of biomarkers to aid diagnosis, inform disease progression trajectories, and allow better targeting of treatments to those patients most likely to respond.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          A common MUC5B promoter polymorphism and pulmonary fibrosis.

          Max A Seibold, Anastasia Wise, Marcy Speer … (2011)
          The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk. Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families. We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression was assessed in lung tissue. Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes. The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P=1.2×10(-15); allelic association with idiopathic pulmonary fibrosis, P=2.5×10(-37)). The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 6.8 (95% confidence interval [CI], 3.9 to 12.0) and 20.8 (95% CI, 3.8 to 113.7), respectively, for familial interstitial pneumonia and 9.0 (95% CI, 6.2 to 13.1) and 21.8 (95% CI, 5.1 to 93.5), respectively, for idiopathic pulmonary fibrosis. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 37.4 times as high as in unaffected subjects homozygous for the wild-type allele, P<0.001). MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis. A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis. Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis. (Funded by the National Heart, Lung, and Blood Institute and others.).
          Article 0 comments Cited 385 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology.

            Lawrence J. Laslett, Peter Alagona, Bernard A Clark … (2012)
            The environment in which the field of cardiology finds itself has been rapidly changing. This supplement, an expansion of a report created for the Board of Trustees, is intended to provide a timely snapshot of the socio-economic, political, and scientific aspects of this environment as it applies to practice both in the United States and internationally. This publication should assist healthcare professionals looking for the most recent statistics on cardiovascular disease and the risk factors that contribute to it, drug and device trends affecting the industry, and how the practice of cardiology is changing in the United States. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
            Article 0 comments Cited 251 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

              Amit Khera, Mark D. Chaffin, Kaitlin H Wade … (2019)
              Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic – the majority of inherited susceptibility is related to the cumulative impact of many common DNA variants. Here, we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in >300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13 kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal difference in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by age 18 years. This new approach to quantify inherited susceptibility to obesity using affords new opportunities for clinical prevention and mechanistic assessment. A genome-wide polygenic score quantifies inherited susceptibility to obesity, integrating information from 2.1 million common genetic variants to identify adults at risk of severe obesity.
              Article 0 comments Cited 239 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Science
                Abbreviated Title: Science
                Publisher: American Association for the Advancement of Science (AAAS)
                ISSN (Print): 0036-8075
                ISSN (Electronic): 1095-9203
                Publication date Created: September 26 2019
                Publication date Created: September 27 2019
                Publication date (Electronic): September 26 2019
                Publication date (Print): September 27 2019
                Volume: 365
                Issue: 6460
                Pages: 1409-1413
                Article
                DOI: 10.1126/science.aax4588
                PubMed ID: 31604268
                SO-VID: a8187cde-4fbf-4441-93da-4b643c538511
                Copyright © © 2019
                License:

                http://www.sciencemag.org/about/science-licenses-journal-article-reuse

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content371

                See all similar

                Cited by70

                See all cited by

                Most referenced authors2,726

                See all reference authors