Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility

• DOI: 10.1038/s41467-018-05537-2
• Publication Date: 2018-08-03T13:56:37Z
• Authors: Mitchell J. Machiela; Thomas G. P. Grün...; Didier Surdez; Stephanie Reynaud; Olivier Mirabeau; Eric Karlins; Rebeca Alba Rubio; Sakina Zaidi; Sandrine Grossete...; Stelly Ballet; Eve Lapouble; Valérie Laurence; Jean Michon; Gaelle Pierron; Heinrich Kovar; Nathalie Gaspar; Udo Kontny; Anna González-Neira; Piero Picci; Javier Alonso; Ana Patino-Garcia; Nadège Corradini; Perrine Marec Bérard; Neal D. Freedman; Nathaniel Rothman; Casey L. Dagnall; Laurie Burdett; Kristine Jones; Michelle Manning; Kathleen Wyatt; Weiyin Zhou; Meredith Yeager; David G. Cox; Robert N. Hoover; Javed Khan; Gregory T. Armstrong; Wendy M. Leisenring; Smita Bhatia; Leslie L. Robison; Andreas E. Kulozik; Jennifer Kriebel; Thomas Meitinger; Markus Metzler; Wolfgang Hartmann; Konstantin Strauch; Thomas Kirchner; Uta Dirksen; Lindsay M. Morton; Lisa Mirabello; Margaret A. Tucker; Franck Tirode; Stephen J. Chanock; Olivier Delattre
• Keywords: Genome-wide Association Study; Genetic architecture; Genetic Association

Abstract Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1 - FLI1 fusion. We performed genome-wide association study of 733 EWS cases and 1346 unaffected individuals European ancestry. Our replicates previously reported susceptibility loci at 1p36.22, 10q21.3 15q15.1, identifies new 6p25.1, 20p11.22 20p11.23. Effect estimates exhibit odds ratios in excess 1.7, which high for GWAS, striking light rarity familial syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes 6p25.1 ( RREB1 ) 20p11.23 KIZ ). The near NKX2-2 , highly overexpressed gene EWS. Interestingly, most reside GGAA repeat sequences may disrupt binding EWSR1-FLI1 fusion protein. to case discovery ratio from suggests genetic architecture moderate risk SNPs constitute significant fraction risk.