Spanish cases and controls assessed by GWAS
Spanish patients were recruited in the Allergy Service, Carlos Haya Hospital, Malaga, Spain. From the initial samples of the 436 patients and 1218 control subjects, 413 and 1124 passed quality control for HLA loci, respectively, and were retained in the final statistical analyses. We used 184 additional control subjects from the same population, which allowed us to perform the association study with 1308 controls. The retained population included 98 cases with delayed hypersensitivity to penicillins diagnosed as previously described18 and 315 cases with immediate allergic reactions from the aforementioned study.11 They ranged from 16 to 60 years old. The 1,308 controls were from Malaga and Salamanca (Spain), as previously described.11 Age- and gender-paired volunteers were recruited in preventive-care consultations. All of them tolerated amoxicillin and other penicillins on different occasions, and they had no histories of allergic, dermatological, or respiratory diseases. Subjects who had never taken penicillins and those with a C-reactive protein blood concentration higher than 5 mg/L were excluded from the control group. All patients and controls were of Caucasian origin. Before allergy tests, all subjects received information about possible related risks, and written informed consent for participating in the study and providing DNA samples was obtained from each patient or the parents of those under 18 years of age. The respective institutional review boards approved the protocol.