Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer. Ruiz-Pinto, S., Pita, G., Patiño-García, A., Alonso, J., Pérez-Martínez, A., Cartón, A. J., Gutiérrez-Larraya, F., Alonso, M. R., Barnes, D. R., Dennis, J., Michailidou, K., Gómez-Santos, C., Thompson, D. J., Easton, D. F., Benítez, J., & González-Neira, A. Pharmacogenetics and Genomics, 27(12):445–453, December, 2017. doi abstract bibtex OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C\textgreaterT, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.
@article{ruiz-pinto_exome_2017,
title = {Exome array analysis identifies {GPR35} as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer},
volume = {27},
issn = {1744-6880},
doi = {10.1097/FPC.0000000000000309},
abstract = {OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients.
PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC.
RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C{\textgreater}T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses.
CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.},
language = {eng},
number = {12},
journal = {Pharmacogenetics and Genomics},
author = {Ruiz-Pinto, Sara and Pita, Guillermo and Patiño-García, Ana and Alonso, Javier and Pérez-Martínez, Antonio and Cartón, Antonio J. and Gutiérrez-Larraya, Federico and Alonso, María R. and Barnes, Daniel R. and Dennis, Joe and Michailidou, Kyriaki and Gómez-Santos, Carmen and Thompson, Deborah J. and Easton, Douglas F. and Benítez, Javier and González-Neira, Anna},
month = dec,
year = {2017},
pmid = {28961156},
keywords = {Adolescent, Anthracyclines, Antineoplastic Agents, Child, Child, Preschool, Exome, Female, Genetic Predisposition to Disease, Heart, Humans, Infant, Leukemia, Male, Osteosarcoma, Receptors, G-Protein-Coupled, Sarcoma, Ewing},
pages = {445--453},
}
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F.","Benítez, J.","González-Neira, A."],"bibdata":{"bibtype":"article","type":"article","title":"Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer","volume":"27","issn":"1744-6880","doi":"10.1097/FPC.0000000000000309","abstract":"OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C\\textgreaterT, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.","language":"eng","number":"12","journal":"Pharmacogenetics and Genomics","author":[{"propositions":[],"lastnames":["Ruiz-Pinto"],"firstnames":["Sara"],"suffixes":[]},{"propositions":[],"lastnames":["Pita"],"firstnames":["Guillermo"],"suffixes":[]},{"propositions":[],"lastnames":["Patiño-García"],"firstnames":["Ana"],"suffixes":[]},{"propositions":[],"lastnames":["Alonso"],"firstnames":["Javier"],"suffixes":[]},{"propositions":[],"lastnames":["Pérez-Martínez"],"firstnames":["Antonio"],"suffixes":[]},{"propositions":[],"lastnames":["Cartón"],"firstnames":["Antonio","J."],"suffixes":[]},{"propositions":[],"lastnames":["Gutiérrez-Larraya"],"firstnames":["Federico"],"suffixes":[]},{"propositions":[],"lastnames":["Alonso"],"firstnames":["María","R."],"suffixes":[]},{"propositions":[],"lastnames":["Barnes"],"firstnames":["Daniel","R."],"suffixes":[]},{"propositions":[],"lastnames":["Dennis"],"firstnames":["Joe"],"suffixes":[]},{"propositions":[],"lastnames":["Michailidou"],"firstnames":["Kyriaki"],"suffixes":[]},{"propositions":[],"lastnames":["Gómez-Santos"],"firstnames":["Carmen"],"suffixes":[]},{"propositions":[],"lastnames":["Thompson"],"firstnames":["Deborah","J."],"suffixes":[]},{"propositions":[],"lastnames":["Easton"],"firstnames":["Douglas","F."],"suffixes":[]},{"propositions":[],"lastnames":["Benítez"],"firstnames":["Javier"],"suffixes":[]},{"propositions":[],"lastnames":["González-Neira"],"firstnames":["Anna"],"suffixes":[]}],"month":"December","year":"2017","pmid":"28961156","keywords":"Adolescent, Anthracyclines, Antineoplastic Agents, Child, Child, Preschool, Exome, Female, Genetic Predisposition to Disease, Heart, Humans, Infant, Leukemia, Male, Osteosarcoma, Receptors, G-Protein-Coupled, Sarcoma, Ewing","pages":"445–453","bibtex":"@article{ruiz-pinto_exome_2017,\n\ttitle = {Exome array analysis identifies {GPR35} as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer},\n\tvolume = {27},\n\tissn = {1744-6880},\n\tdoi = {10.1097/FPC.0000000000000309},\n\tabstract = {OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients.\nPATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC.\nRESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C{\\textgreater}T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses.\nCONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {Pharmacogenetics and Genomics},\n\tauthor = {Ruiz-Pinto, Sara and Pita, Guillermo and Patiño-García, Ana and Alonso, Javier and Pérez-Martínez, Antonio and Cartón, Antonio J. and Gutiérrez-Larraya, Federico and Alonso, María R. and Barnes, Daniel R. and Dennis, Joe and Michailidou, Kyriaki and Gómez-Santos, Carmen and Thompson, Deborah J. and Easton, Douglas F. and Benítez, Javier and González-Neira, Anna},\n\tmonth = dec,\n\tyear = {2017},\n\tpmid = {28961156},\n\tkeywords = {Adolescent, Anthracyclines, Antineoplastic Agents, Child, Child, Preschool, Exome, Female, Genetic Predisposition to Disease, Heart, Humans, Infant, Leukemia, Male, Osteosarcoma, Receptors, G-Protein-Coupled, Sarcoma, Ewing},\n\tpages = {445--453},\n}\n\n\n\n\n\n\n\n","author_short":["Ruiz-Pinto, S.","Pita, G.","Patiño-García, A.","Alonso, J.","Pérez-Martínez, A.","Cartón, A. 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