Variants in BANK1are associated with lupus nephritis of European ancestry

The genetic background of lupus nephritis (LN) has not been completely elucidated. We performed a case-only study of 2886 SLE patients, including 947 (33%) with LN. Renal biopsies were available from 396 patients. The discovery cohort (Sweden, n= 1091) and replication cohort 1 (US, n= 962) were genotyped on the Immunochip and replication cohort 2 (Denmark/Norway, n= 833) on a custom array. Patients with LN, proliferative nephritis, or LN with end-stage renal disease were compared with SLE without nephritis. Six loci were associated with LN (p< 1 × 10−4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y,and ACER3) in the discovery cohort. Variants in BANK1showed the strongest association with LN in replication cohort 1 (p= 9.5 × 10−4) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1and LN in replication cohort 2 (p= 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p= 2.2 × 10−7). DNA methylation data in 180 LN patients demonstrated methylation quantitative trait loci (meQTL) effects between a CpG site and BANK1variants. To conclude, we describe genetic variations in BANK1associated with LN and evidence for genetic regulation of DNA methylation within the BANK1locus. This indicates a role for BANK1in LN pathogenesis.