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Variants in BANK1 are associated with lupus nephritis of European ancestry

Bolin, Karin ; Imgenberg-Kreuz, Juliana ; Leonard, Dag ; Sandling, Johanna K. ; Alexsson, Andrei ; Pucholt, Pascal ; Haarhaus, Malena Loberg ; Almlöf, Jonas Carlsson ; Nititham, Joanne and Jönsen, Andreas LU , et al. (2021) In Genes and Immunity 22(3). p.194-202
Abstract

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 ×... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes and Immunity
volume
22
issue
3
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:34127828
  • scopus:85107861880
ISSN
1466-4879
DOI
10.1038/s41435-021-00142-8
language
English
LU publication?
yes
id
791abca4-5954-49ea-9474-809f6a58bbd5
date added to LUP
2021-08-03 09:53:35
date last changed
2024-04-20 08:46:58
@article{791abca4-5954-49ea-9474-809f6a58bbd5,
  abstract     = {{<p>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 &lt; 1 × 10<sup>−4</sup>, 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<sup>−4</sup>) 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<sup>−7</sup>). 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.</p>}},
  author       = {{Bolin, Karin and Imgenberg-Kreuz, Juliana and Leonard, Dag and Sandling, Johanna K. and Alexsson, Andrei and Pucholt, Pascal and Haarhaus, Malena Loberg and Almlöf, Jonas Carlsson and Nititham, Joanne and Jönsen, Andreas and Sjöwall, Christopher and Bengtsson, Anders A. and Rantapää-Dahlqvist, Solbritt and Svenungsson, Elisabet and Gunnarsson, Iva and Syvänen, Ann Christine and Lerang, Karoline and Troldborg, Anne and Voss, Anne and Molberg, Øyvind and Jacobsen, Søren and Criswell, Lindsey and Rönnblom, Lars and Nordmark, Gunnel}},
  issn         = {{1466-4879}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{3}},
  pages        = {{194--202}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Genes and Immunity}},
  title        = {{Variants in BANK1 are associated with lupus nephritis of European ancestry}},
  url          = {{http://dx.doi.org/10.1038/s41435-021-00142-8}},
  doi          = {{10.1038/s41435-021-00142-8}},
  volume       = {{22}},
  year         = {{2021}},
}