biostudies-literatureMcDaniel LDNICHD NIH HHSNational Cancer InstituteNCI NIH HHSRosetreesWellcome Truste1006787https://www.ebi.ac.uk/biostudies/studies/S-EPMC5456408biostudies-literatureUnknown13(5)Neuroblastoma is a cancer of the developing sympathetic nervous system that most commonly presents in young children and accounts for approximately 12% of pediatric oncology deaths. Here, we report on a genome-wide association study (GWAS) in a discovery cohort or 2,101 cases and 4,202 controls of European ancestry. We identify two new association signals at 3q25 and 4p16 that replicated robustly in multiple independent cohorts comprising 1,163 cases and 4,396 controls (3q25: rs6441201 combined P = 1.2x10-11, Odds Ratio 1.23, 95% CI:1.16-1.31; 4p16: rs3796727 combined P = 1.26x10-12, Odds Ratio 1.30, 95% CI: 1.21-1.40). The 4p16 signal maps within the carboxypeptidase Z (CPZ) gene. The 3q25 signal resides within the arginine/serine-rich coiled-coil 1 (RSRC1) gene and upstream of the myeloiPLoS geneticsCommon variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.PMC5456408P30 HD026979M28-F1-CD2R01 CA204974100210/Z/12/ZR00 CA151869R01 CA124709M28-F2R01-CA124709R00-CA151869Oldridge DAMcDaniel LDCapasso MConkrite KLRahman NChang XDevoto MHakonarson HDiskin SJVaksman ZDiamond MIolascon AHou CHorn MZachariou AfalseCommon variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.Neuroblastoma is a cancer of the developing sympathetic nervous system that most commonly presents in young children and accounts for approximately 12% of pediatric oncology deaths. Here, we report on a genome-wide association study (GWAS) in a discovery cohort or 2,101 cases and 4,202 controls of European ancestry. We identify two new association signals at 3q25 and 4p16 that replicated robustly in multiple independent cohorts comprising 1,163 cases and 4,396 controls (3q25: rs6441201 combined P = 1.2x10-11, Odds Ratio 1.23, 95% CI:1.16-1.31; 4p16: rs3796727 combined P = 1.26x10-12, Odds Ratio 1.30, 95% CI: 1.21-1.40). The 4p16 signal maps within the carboxypeptidase Z (CPZ) gene. The 3q25 signal resides within the arginine/serine-rich coiled-coil 1 (RSRC1) gene and upstream of the myeloi2017-01-01T00:00:00Z2017 May2026-05-03T19:08:21.037Z2025-05-29T21:57:49.374ZS-EPMC54564082854512810.1371/journal.pgen.1006787