haplotype that was associated with protection in late stages of a chronic disease that involves both bone and cartilage, may have a different or no effect on early disease initiation. A substantial part of the variance in clinical expression of OA is attributed to genetics,1 and multiple SNPs have been associ- ated with OA susceptibility.25 Few studies have evaluated the role of genetic factors in severity or progression of knee OA,26 27 and, other than our report, we are not aware of genetic markers for knee OA severity validated in a second population. The IL1RN CTA haplotype appears to identify a substantial segment of patients with knee OA who are at low risk for severe destruction, and the data suggest that IL1 biological activity is a determinant of knee OA severity. Biomarkers that identify patients more likely to develop severe disease should expedite successful development of disease-modifying OA drugs and improvements in medical and surgical management of knee OA. Acknowledgements We greatly appreciate the genotyping expertise provided by Kerry Chios, Julie Samia and Gary Breton, and input on data interpretation by Sir Gordon Duff. Funding This study was funded in part by the following grants: grant from Interleukin Genetics to NYUHJD; NIH grant: RO1 AR052873-01 to NYUHJD; NIH grant: U01 AR050898 to Duke University. Competing interests When the research was conducted JFB, and KSK were full- time employees and H-YW was a part-time consultant for Interleukin Genetics. Patient consent Obtained. Ethics approval This study was conducted with the approval of the NYU institutional review board. Contributors The study concept, design was developed by SBA, KK, JB and MA. Data and statistical analysis was performed by NA, KK, VK and H-YH. Patient recruitment and clinical data collection were performed by SK, JS, JGB, GM and VK. The manuscript was drafted and critically checked by KK, NA, SA, VK and MA. 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