DataSheet_1_GSTM1 Copy Number Is Not Associated With Risk of Kidney Failure in a Large Cohort.docx

Deletion of glutathione S-transferase µ1 (GSTM1) is common in populations and has been asserted to associate with chronic kidney disease progression in some research studies. The association needs to be validated. We estimated GSTM1 copy number using whole exome sequencing data in the DiscovEHR cohort. Kidney failure was defined as requiring dialysis or receiving kidney transplant using data from the electronic health record and linkage to the United States Renal Data System, or the most recent eGFR < 15 ml/min/1.73 m2. In a cohort of 46,983 unrelated participants, 28.8% of blacks and 52.1% of whites had 0 copies of GSTM1. Over a mean of 9.2 years follow-up, 645 kidney failure events were observed in 46,187 white participants, and 28 in 796 black participants. No significant association was observed between GSTM1 copy number and kidney failure in Cox regression adjusting for age, sex, BMI, smoking status, genetic principal components, or comorbid conditions (hypertension, diabetes, heart failure, coronary artery disease, and stroke), whether using a genotypic, dominant, or recessive model. In sensitivity analyses, GSTM1 copy number was not associated with kidney failure in participants that were 45 years or older at baseline, had baseline eGFR < 60 ml/min/1.73 m2, or with baseline year between 1996 and 2002. In conclusion, we found no association between GSTM1 copy number and kidney failure in a large cohort study.