Variants in BANK1 are associated with lupus nephritis of European ancestry.

Bolin K, Imgenberg-Kreuz J, Leonard D, Sandling JK, Alexsson A, Pucholt P, Haarhaus ML, Almlöf JC, Nititham J, Jönsen A, Sjöwall C, Bengtsson AA, Rantapää-Dahlqvist S, Svenungsson E, Gunnarsson I, Syvänen AC, Lerang K, Troldborg A, Voss A, Molberg Ø, Jacobsen S, Criswell L, Rönnblom L, Nordmark G

Genes Immun. 22 (3) 194-202 [2021-07-00; online 2021-06-14]

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.

NGI Uppsala (SNP&SEQ Technology Platform)

National Genomics Infrastructure

QC bibliography QC xrefs

PubMed 34127828

DOI 10.1038/s41435-021-00142-8

Crossref 10.1038/s41435-021-00142-8

pii: 10.1038/s41435-021-00142-8
pmc: PMC8277572