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 BANK1 showed 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 BANK1 and 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 BANK1 variants. To conclude, we describe genetic variations in BANK1 associated with LN and evidence for genetic regulation of DNA methylation within the BANK1 locus. This indicates a role for BANK1 in LN pathogenesis.

狼疮性肾炎 (LN) 的遗传背景尚未完全阐明。我们对 2886 名 SLE 患者进行了一项仅病例研究，其中 947 名 (33%) 患有 LN。可从 396 名患者进行肾活检。发现队列（瑞典，n  = 1091）和复制队列 1（美国，n  = 962）在免疫芯片上进行了基因分型，复制队列 2（丹麦/挪威，n  = 833）在定制阵列上进行了基因分型。将患有 LN、增殖性肾炎或 LN 伴终末期肾病的患者与无肾炎的 SLE 患者进行比较。六个位点与 LN 相关（p  < 1 × 10 ^-4、NFKBIA、CACNA1S、ITGA1、BANK1、OR2Y和ACER3) 在发现队列中。BANK1中的变体在复制队列 1 ( p  = 9.5 × 10 ^-4 ) 中与 LN 以及发现和复制队列 1 的荟萃分析中的增殖性肾炎显示出最强的关联。在复制队列 2 中BANK1和 LN之间存在弱关联( p  = 0.052)，并且在所有三个队列的荟萃分析中，该关联得到加强 ( p  = 2.2 × 10 ^-7 )。180 名 LN 患者的 DNA 甲基化数据证明了 CpG 位点和BANK1变体之间的甲基化数量性状位点 (meQTL) 效应。总之，我们描述了BANK1中的遗传变异与 LN 相关，以及BANK1基因座内 DNA 甲基化遗传调控的证据。这表明BANK1在 LN 发病机制中的作用。