@article{OcakDrechslerVossenetal.2014,
  author    = {Ocak, Gurbey and Drechsler, Christiane and Vossen, Carla Y. and Vos, Hans L. and Rosendaal, Frits R. and Reitsma, Pieter H. and Hoffmann, Michael M. and M{\"a}rz, Winfried and Ouwehand, Willem H. and Krediet, Raymond T. and Boeschoten, Elisabeth W. and Dekker, Frido W. and Wanner, Christoph and Verduijn, Marion},
  title     = {Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {5},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0097251},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116265},
  pages     = {e97251},
  year      = {2014},
  abstract  = {Background: The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients. Methods: Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort. Results: Factor V Leiden was associated with a 1.5-fold (95\% CI 1.1-1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95\% CI 1.0-1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality. Conclusion: Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.},
  language  = {en}
}
@article{WestburyTurroGreeneetal.2015,
  author    = {Westbury, Sarah K and Turro, Ernest and Greene, Daniel and Lentaigne, Claire and Kelly, Anne M and Bariana, Tadbir K and Simeoni, Ilenia and Pillois, Xavier and Attwood, Antony and Austin, Steve and Jansen, Sjoert BG and Bakchoul, Tamam and Crisp-Hihn, Abi and Erber, Wendy N and Favier, R{\´e}mi and Foad, Nicola and Gattens, Michael and Jolley, Jennifer D and Liesner, Ri and Meacham, Stuart and Millar, Carolyn M and Nurden, Alan T and Peerlinck, Kathelijne and Perry, David J and Poudel, Pawan and Schulman, Sol and Schulze, Harald and Stephens, Jonathan C and Furie, Bruce and Robinson, Peter N and van Geet, Chris and Rendon, Augusto and Gomez, Keith and Laffan, Michael A and Lambert, Michele P and Nurden, Paquita and Ouwehand, Willem H and Richardson, Sylvia and Mumford, Andrew D and Freson, Kathleen},
  title     = {Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders},
  series = {Genome Medicine},
  volume    = {7},
  journal   = {Genome Medicine},
  number    = {36},
  doi       = {10.1186/s13073-015-0151-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143329},
  year      = {2015},
  abstract  = {Background: Heritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases. Methods: We report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms. Cluster analyses are then used to characterise groups of cases with similar HPO terms and variants in the same genes. Results: We show that 60\% of index cases with heritable BPD enrolled at 10 European or US centres were annotated with HPO terms indicating abnormalities in organ systems other than blood or blood-forming tissues, particularly the nervous system. Cases within pedigrees clustered closely together on the bases of their HPO-coded phenotypes, as did cases sharing several clinically suspected syndromic disorders. Cases subsequently found to harbour variants in ACTN1 also clustered closely, even though diagnosis of this recently described disorder was not possible using only the clinical and laboratory data available to the enrolling clinician. Conclusions: These findings validate our novel HPO-based phenotype clustering methodology for known BPD, thus providing a new discovery tool for BPD of unknown genetic basis. This approach will also be relevant for other rare diseases with significant genetic heterogeneity.},
  language  = {en}
}