Mechanistic phenotypes: An aggregative phenotyping strategy to identify disease mechanisms using GWAS data

PLoS ONE

Volumn 8, Issue 12, 2013, Pages

  Mosley, Jonathan D ^a   Van Driest, Sara L ^a   Larkin, Emma K ^a   Weeke, Peter E ^a   Witte, John S ^b   Wells, Quinn S ^a   Karnes, Jason H ^a   Guo, Yan ^c   Bastarache, Lisa ^a   Olson, Lana M ^d   McCarty, Catherine A ^e   Pacheco, Jennifer A ^f   Jarvik, Gail P ^g   Carrell, David S ^h   Larson, Eric B ^h   Crosslin, David R ^g   Kullo, Iftikhar J ⁱ   Tromp, Gerard ^j   Kuivaniemi, Helena ^j   Carey, David J ^j   Ritchie, Marylyn D ^k   Denny, Josh C ^a   Roden, Dan M ^a   more..

^a VANDERBILT UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^e ESSENTIA INSTITUTE OF RURAL HEALTH   (United States)

^f NORTHWESTERN UNIVERSITY   (United States)

^g UNIVERSITY OF WASHINGTON   (United States)

^h GROUP HEALTH RESEARCH INSTITUTE   (United States)

ⁱ MAYO CLINIC   (United States)

^j WEIS CENTER FOR RESEARCH   (United States)

^k PENNSYLVANIA STATE UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; AFRICAN AMERICAN; ANALYTIC METHOD; ARTICLE; BLOOD CLOTTING; CANCER DIAGNOSIS; CANCER GENETICS; CARCINOGENESIS; CAUCASIAN; CHD1L GENE; CHROMATID; CHROMOSOME SEGREGATION; CONTROLLED STUDY; DISEASE COURSE; DNA REPAIR; EUROPEAN AMERICAN; F2RL2 GENE; F5 GENE; FANCA GENE; FANCI GENE; FANCP GENE; FEMALE; FUNCTIONAL GENOMICS; GENE; GENETIC ASSOCIATION; GENETIC MODEL; GENETIC RISK; GENETIC VARIABILITY; GENOMIC INSTABILITY; HUMAN; KIF25 GENE; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; MIDDLE AGED; ONTOLOGY; P2RY12 GENE; PHENOTYPE; PINX1 GENE; POLG GENE; POPULATION GENETICS; POPULATION RESEARCH; SINGLE NUCLEOTIDE POLYMORPHISM; SLX4 GENE; THROMBOSIS; TUMOR SUPPRESSOR GENE; XRCC1 GENE;

ELECTRONIC HEALTH RECORDS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84892565751     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0081503     Document Type: Article

References (39)

1. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, et al. (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96: 261-268.
2. Foulkes WD (2008) Inherited susceptibility to common cancers. N Engl J Med 359: 2143-2153. doi:10.1056/NEJMra0802968.
3. Seligsohn U, Lubetsky A (2001) Genetic Susceptibility to Venous Thrombosis. New England Journal of Medicine 344: 1222-1231. doi:10.1056/ NEJM200104193441607.
4. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747-753. doi:10.1038/nature08494.
5. Klei L, Luca D, Devlin B, Roeder K (2008) Pleiotropy and principal components of heritability combine to increase power for association analysis. Genet Epidemiol 32: 9-19. doi:10.1002/gepi.20257.
6. Fitzmaurice GM, Laird NM (1993) A likelihood-based method for analysing longitudinal binary responses. Biometrika 80: 141-151. doi:10.1093/biomet/80.1. 141.
7. Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38: 963-974.
8. Liu J, Pei Y, Papasian CJ, Deng H-W (2009) Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equations. Genet Epidemiol 33: 217-227. doi:10.1002/gepi.20372.
9. Yang Q, Wang Y (2012) Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies. Journal of Probability and Statistics 2012: 1-13. doi:10.1155/2012/652569.
10. Manis JP (2007) Knock out, knock in, knock down - genetically manipulated mice and the Nobel Prize. N Engl J Med 357: 2426-2429. doi:10.1056/ NEJMp0707712.
11. Denny JC, Ritchie MD, Basford MA, Pulley JM, Bastarache L, et al. (2010) PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations. Bioinformatics 26: 1205-1210. doi:10.1093/ bioinformatics/btq126.
12. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354: 1264-1272. doi:10.1056/NEJMoa054013.
13. Jenkins RB, Xiao Y, Sicotte H, Decker PA, Kollmeyer TM, et al. (2012) A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 44: 1122-1125. doi:10.1038/ng.2388.
14. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, et al. (2012) A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488: 96-99. doi:10.1038/nature11283.
15. Roden DM, Pulley JM, Basford MA, Bernard GR, Clayton EW, et al. (2008) Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther 84: 362-369. doi:10.1038/clpt.2008.89.
16. McCarty CA, Chisholm RL, Chute CG, Kullo IJ, Jarvik GP, et al. (2011) The eMERGE Network: a consortium of biorepositories linked to electronic medical records data for conducting genomic studies. BMC Med Genomics 4: 13. doi:10.1186/1755-8794-4-13.
17. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155: 945-959.
18. Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, et al. (2003) DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4: P3.
19. Gottesman O, Kuivaniemi H, Tromp G, Faucett WA, Li R, et al. (2013) The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future. Genet Med 15: 761-771. doi:10.1038/gim.2013.72.
20. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559-575. doi:10.1086/519795.
21. Cramer TJ, Gale AJ (2012) The anticoagulant function of coagulation factor V. Thromb Haemost 107: 15-21. doi:10.1160/TH11-06-0431.
22. Andre P, Delaney SM, LaRocca T, Vincent D, DeGuzman F, et al. (2003) P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest 112: 398-406. doi:10.1172/JCI17864.
23. Coughlin SR (2005) Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 3: 1800-1814. doi:10.1111/j.1538-7836. 2005.01377.x.
24. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674. doi:10.1016/j.cell.2011.02.013.
25. Chan THM, Chen L, Liu M, Hu L, Zheng B, et al. (2012) Translationally controlled tumor protein induces mitotic defects and chromosome missegregation in hepatocellular carcinoma development. Hepatology 55: 491-505. doi:10.1002/hep.24709.
26. Fekairi S, Scaglione S, Chahwan C, Taylor ER, Tissier A, et al. (2009) Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138: 78-89. doi:10.1016/j.cell.2009.06. 029.
27. Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, et al. (2001) XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 104: 107-117.
28. Eyfjord JE, Bodvarsdottir SK (2005) Genomic instability and cancer: networks involved in response to DNA damage. Mutat Res 592: 18-28. doi:10.1016/j.mrfmmm.2005.05.010.
29. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27: 247-254. doi:10.1038/85798.
30. Okamoto S, Matsushima M, Nakamura Y (1998) Identification, genomic organization, and alternative splicing of KNSL3, a novel human gene encoding a kinesin-like protein. Cytogenet Cell Genet 83: 25-29. doi:15159.
31. Yonekawa T, Yang S, Counter CM (2012) PinX1 localizes to telomeres and stabilizes TRF1 at mitosis. Mol Cell Biol 32: 1387-1395. doi:10.1128/MCB.05641- 11.
32. Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, et al. (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381: 1371-1379. doi:10.1016/S0140- 6736(12)62129-1.
33. Negrini S, Gorgoulis VG, Halazonetis TD (2010) Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11: 220-228. doi:10.1038/nrm2858.
34. Kottemann MC, Smogorzewska A (2013) Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493: 356-363. doi:10.1038/nature11863.
35. Cookson WO (1999) Disease taxonomy - polygenic. Br Med Bull 55: 358-365.
36. Wagner GP, Zhang J (2011) The pleiotropic structure of the genotypephenotype map: the evolvability of complex organisms. Nat Rev Genet 12: 204-213. doi:10.1038/nrg2949.
37. Shah NH, Cole T, Musen MA (2012) Chapter 9: Analyses using disease ontologies. PLoS Comput Biol 8: e1002827. doi:10.1371/journal.pcbi.1002827.
38. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57-70.
39. Cerhan JR, Fredericksen ZS, Novak AJ, Ansell SM, Kay NE, et al. (2012) A two-stage evaluation of genetic variation in immune and inflammation genes with risk of non-hodgkin lymphoma identifies new susceptibility locus in 6p21.3 region. Cancer Epidemiol Biomarkers Prev 21: 1799-1806. doi:10.1158/1055-9965. EPI-12-0696.