Supplementary Material for: Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease

<br><strong><em>Background:</em></strong> The reticulon 1 gene <i>(RTN1)</i> encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression. <b><i>Methods:</i></b><i>RTN1</i> single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. <i>RTN1</i> SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n = 1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls. <b><i>Results:</i></b> Three intronic <i>RTN1</i> variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery + replication) p values were 0.015-3.0 × 10<sup>-4</sup> (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p = 0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p = 6.7 × 10<sup>-4</sup>, OR 0.73) and rs12431381 (p = 7.5 × 10<sup>-4</sup>, OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p = 0.032 AAs; p = 0.048 EAs). <b><i>Conclusions:</i></b> These results suggest evidence of genetic association between common variants in <i>RTN1</i> and ESKD in AAs and EAs.