AIM: Pharmacogenomics holds promise to rationalize drug use by minimizing drug toxicity and at the same time increase drug efficacy. There are currently several assays to screen for known pharmacogenomic biomarkers for the most commonly prescribed drugs. However, these genetic screening assays cannot account for other known or novel pharmacogenomic markers. MATERIALS & METHODS: We analyzed whole-genome sequences of 482 unrelated individuals of various ethnic backgrounds to obtain their personalized pharmacogenomics profiles. RESULTS: Bioinformatics analysis revealed 408,964 variants in 231 pharmacogenes, from which 26,807 were residing on exons and proximal regulatory sequences, whereas 16,487 were novel. In silico analyses indicated that 1012 novel pharmacogene-related variants possibly abolish protein function. We have also performed whole-genome sequencing analysis in a seven-member family of Greek origin in an effort to explain the variable response rate to acenocoumarol treatment in two family members. CONCLUSION: Overall, our data demonstrate that whole-genome sequencing, unlike conventional genetic screening methods, is necessary to determine an individual's pharmacogenomics profile in a more comprehensive manner, which, combined with the gradually decreasing whole-genome sequencing costs, would expedite bringing personalized medicine closer to reality.
AIM: Pharmacogenomics holds promise to rationalize drug use by minimizing drug toxicity and at the same time increase drug efficacy. There are currently several assays to screen for known pharmacogenomic biomarkers for the most commonly prescribed drugs. However, these genetic screening assays cannot account for other known or novel pharmacogenomic markers. MATERIALS & METHODS: We analyzed whole-genome sequences of 482 unrelated individuals of various ethnic backgrounds to obtain their personalized pharmacogenomics profiles. RESULTS: Bioinformatics analysis revealed 408,964 variants in 231 pharmacogenes, from which 26,807 were residing on exons and proximal regulatory sequences, whereas 16,487 were novel. In silico analyses indicated that 1012 novel pharmacogene-related variants possibly abolish protein function. We have also performed whole-genome sequencing analysis in a seven-member family of Greek origin in an effort to explain the variable response rate to acenocoumarol treatment in two family members. CONCLUSION: Overall, our data demonstrate that whole-genome sequencing, unlike conventional genetic screening methods, is necessary to determine an individual's pharmacogenomics profile in a more comprehensive manner, which, combined with the gradually decreasing whole-genome sequencing costs, would expedite bringing personalized medicine closer to reality.
Authors: Teri A Manolio; Marc Abramowicz; Fahd Al-Mulla; Warwick Anderson; Rudi Balling; Adam C Berger; Steven Bleyl; Aravinda Chakravarti; Wasun Chantratita; Rex L Chisholm; Vajira H W Dissanayake; Michael Dunn; Victor J Dzau; Bok-Ghee Han; Tim Hubbard; Anne Kolbe; Bruce Korf; Michiaki Kubo; Paul Lasko; Erkki Leego; Surakameth Mahasirimongkol; Partha P Majumdar; Gert Matthijs; Howard L McLeod; Andres Metspalu; Pierre Meulien; Satoru Miyano; Yaakov Naparstek; P Pearl O'Rourke; George P Patrinos; Heidi L Rehm; Mary V Relling; Gad Rennert; Laura Lyman Rodriguez; Dan M Roden; Alan R Shuldiner; Sukdeb Sinha; Patrick Tan; Mats Ulfendahl; Robyn Ward; Marc S Williams; John E L Wong; Eric D Green; Geoffrey S Ginsburg Journal: Sci Transl Med Date: 2015-06-03 Impact factor: 17.956
Authors: Semra Şardaş; Laszlo Endrenyi; Ulvi K Gürsoy; Mara Hutz; Biaoyang Lin; George P Patrinos; Lotte M G Steuten; Wei Wang; Louise Warnich; Vural Özdemir Journal: OMICS Date: 2014-10-29
Authors: L V Kalman; Jag Agúndez; M Lindqvist Appell; J L Black; G C Bell; S Boukouvala; C Bruckner; E Bruford; K Caudle; S A Coulthard; A K Daly; Al Del Tredici; J T den Dunnen; K Drozda; R E Everts; D Flockhart; R R Freimuth; A Gaedigk; H Hachad; T Hartshorne; M Ingelman-Sundberg; T E Klein; V M Lauschke; D R Maglott; H L McLeod; G A McMillin; U A Meyer; D J Müller; D A Nickerson; W S Oetting; M Pacanowski; V M Pratt; M V Relling; A Roberts; W S Rubinstein; K Sangkuhl; M Schwab; S A Scott; S C Sim; R K Thirumaran; L H Toji; R F Tyndale; Rhn van Schaik; M Whirl-Carrillo; Ktj Yeo; U M Zanger Journal: Clin Pharmacol Ther Date: 2015-11-20 Impact factor: 6.875
Authors: Judit Kumuthini; Mamana Mbiyavanga; Emile R Chimusa; Jyotishman Pathak; Panu Somervuo; Ron Hn Van Schaik; Vita Dolzan; Clint Mizzi; Kusha Kalideen; Raj S Ramesar; Milan Macek; George P Patrinos; Alessio Squassina Journal: Pharmacogenomics Date: 2016-08-22 Impact factor: 2.533
Authors: George P Patrinos; Emmanouil Pasparakis; Erasmia Koiliari; Alexandre C Pereira; Tábita Hünemeier; Lygia V Pereira; Christina Mitropoulou Journal: Am J Hum Genet Date: 2020-10-01 Impact factor: 11.025
Authors: Kimberly Harding; Tesfaye B Mersha; Fern A Webb; Joseph A Vassalotti; Susanne B Nicholas Journal: Am J Nephrol Date: 2017-08-05 Impact factor: 3.754