Link to dataset related to article "X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis"

メタデータ

公開日
2021-12-23
DOI
  • 10.5281/zenodo.5802017
  • 10.5281/zenodo.5802018
公開者
Zenodo
データ作成者 (e-Rad)
  • Asselta, Rosanna
  • Paraboschi, Elvezia Maria
  • Gerussi, Alessio
  • Cordell, Heather J
  • Mells, George F
  • Sandford, Richard N
  • Jones, David E
  • Nakamura, Minoru
  • Ueno, Kazuko
  • Hitomi, Yuki
  • Kawashima, Minae
  • Nishida, Nao
  • Tokunaga, Katsushi
  • Nagasaki, Masao
  • Tanaka, Atsushi
  • Tang, Ruqi
  • Li, Zhiqiang
  • Shi, Yongyong
  • Liu, Xiangdong
  • Xiong, Ma
  • Hirschfield, Gideon
  • Siminovitch, Katherine A
  • Canadian-US PBC Consortium
  • Italian PBC Genetics Study Group
  • UK-PBC Consortium
  • Japan PBC-GWAS Consortium
  • Carbone, Marco
  • Cardamone, Giulia
  • Duga, Stefano
  • Gershwin, Eric
  • Seldin, Michael F
  • Invernizzi, Pietro

説明

Link to dataset related to article "X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis" Abstract Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 �� 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 �� 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 �� 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 �� 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

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