Link to dataset related to article "X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis"
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- Asselta, Rosanna
- 作成者
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- Gerussi, Alessio
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- Mells, George F
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- Jones, David E
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- Nakamura, Minoru
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- Ueno, Kazuko
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- Hitomi, Yuki
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- Kawashima, Minae
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- Nishida, Nao
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- Nagasaki, Masao
- 作成者
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- Tanaka, Atsushi
- 作成者
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- Tang, Ruqi
- 作成者
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- Li, Zhiqiang
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- Shi, Yongyong
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- Liu, Xiangdong
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- Xiong, Ma
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- Carbone, Marco
- 作成者
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- Duga, Stefano
- 作成者
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- Gershwin, Eric
- 作成者
メタデータ
- 公開日
- 2021-12-23
- DOI
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- 10.5281/zenodo.5802017
- 10.5281/zenodo.5802018
- 公開者
- Zenodo
- データ作成者 (e-Rad)
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- 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.