Genome-wide analysis and characterization of an online sarcoma cohort.

Abstract

10097 Background: Recruitment of an adequately sized cohort for genome-wide studies presents a serious challenge for rare diseases such as sarcoma. Traditional barriers to participation include proximity of clinical centers and motivation or ability to travel. 23andMe’s web-based platform provides increased accessibility to research participation, facilitating rapid recruitment of patients (pts) and enabling a large-scale genome-wide association study (GWAS) of sarcoma. Methods: Sarcoma pts were recruited through web and email campaigns, patient advocacy groups, physician offices, and events. Pts provide IRB-approved consent, complete surveys, and receive updates about research progress through an online account. In collaboration with an uncompensated panel of academic experts, an online survey was developed to collect patient-reported data on diagnosis, family history, symptoms and treatment. Results: This web-based approach has accrued the largest genotyped, recontactable sarcoma cohort to date. In 20 months, 772 sarcoma pts have enrolled, 683 have been genotyped and 611 have provided data online. The cohort is primarily of European ancestry (92%), disproportionately female (72%), with an average age of 51 (± 15 years). More than 88% of pts indicated a soft tissue sarcoma diagnosis, with leiomyosarcoma, liposarcoma and “malignant fibrous histiocytoma” being the most commonly reported subtypes. Over 36% of pts report undergoing active treatment of some type. Association scans were conducted across a set of 8,058,452 imputed SNPs, using 568 unrelated sarcoma cases of European ancestry and >70,000 unrelated population controls from the 23andMe database. Initial results have identified no significant genome-wide associations for general sarcoma risk, despite having >90% power to detect risk variants with >5% minor allele frequency and odds ratio >2.5, suggesting the absence of common variants with strong shared effects across sarcoma subtypes. Conclusions: This pilot study demonstrates feasibility of rapid recruitment and longitudinal engagement of pts through online technology. Such techniques may significantly accelerate, and in some cases fully enable, large-scale genomic studies of sarcoma and other rare diseases.