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3. Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis

Author

Ellis, Justine A., Scurrah, Katrina J., Li, Yun R., Ponsonby, Anne-Louise, Chavez, Raul A., Pezic, Angela, Dwyer, Terence, Akikusa, Jonathan D., Allen, Roger C., Becker, Mara L., Thompson, Susan D., Lie, Benedicte A., Flatø, Berit, Førre, Øystein, Punaro, Marilynn, Wise, Carol, Finkel, Terri H., Hakonarson, Hakon, and Munro, Jane E.

Published
2015
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4. Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis

Author

Li, Jin, primary, Li, Yun R., additional, Glessner, Joseph T., additional, Yang, Jie, additional, March, Michael E., additional, Kao, Charlly, additional, Vaccaro, Courtney N., additional, Bradfield, Jonathan P., additional, Li, Junyi, additional, Mentch, Frank D., additional, Qu, Hui‐Qi, additional, Qi, Xiaohui, additional, Chang, Xiao, additional, Hou, Cuiping, additional, Abrams, Debra J., additional, Qiu, Haijun, additional, Wei, Zhi, additional, Connolly, John J., additional, Wang, Fengxiang, additional, Snyder, James, additional, Flatø, Berit, additional, Thompson, Susan D., additional, Langefeld, Carl D., additional, Lie, Benedicte A., additional, Munro, Jane E., additional, Wise, Carol, additional, Sleiman, Patrick M. A., additional, and Hakonarson, Hakon, additional

Published
2022
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6. High levels of psychosocial distress among Australian frontline healthcare workers during the COVID-19 pandemic: a cross-sectional survey

Author

Smallwood, Natasha, primary, Karimi, Leila, additional, Bismark, Marie, additional, Putland, Mark, additional, Johnson, Douglas, additional, Dharmage, Shyamali Chandrika, additional, Barson, Elizabeth, additional, Atkin, Nicola, additional, Long, Claire, additional, Ng, Irene, additional, Holland, Anne, additional, Munro, Jane E, additional, Thevarajan, Irani, additional, Moore, Cara, additional, McGillion, Anthony, additional, Sandford, Debra, additional, and Willis, Karen, additional

Published
2021
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8. Genomic risk scores for juvenile idiopathic arthritis and its subtypes

Author

Cánovas, Rodrigo, primary, Cobb, Joanna, additional, Brozynska, Marta, additional, Bowes, John, additional, Li, Yun R, additional, Smith, Samantha Louise, additional, Hakonarson, Hakon, additional, Thomson, Wendy, additional, Ellis, Justine A, additional, Abraham, Gad, additional, Munro, Jane E, additional, and Inouye, Michael, additional

Published
2020
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9. Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci

Author

Li, Yun R., primary, Li, Jin, additional, Glessner, Joseph T., additional, Yang, Jie, additional, March, Michael E., additional, Kao, Charlly, additional, Bradfield, Jonathan P., additional, Li, Junyi, additional, Mentch, Frank D., additional, Qu, Huiqi, additional, Qi, Xiaohui, additional, Chang, Xiao, additional, Hou, Cuiping, additional, Abrams, Debra J., additional, Qiu, Haijun, additional, Wei, Zhi, additional, Connolly, John J., additional, Wang, Fengxiang, additional, Snyder, James, additional, Limou, Sophie, additional, Flatø, Berit, additional, Førr, Øystein, additional, Thompson, Susan D., additional, Langefeld, Carl D, additional, Glass, David N, additional, Becker, Mara L., additional, Perez, Elena, additional, Lie, Benedicte A., additional, Punaro, Marilynn, additional, Shivers, Debra K, additional, Ellis, Justine A., additional, Munro, Jane E., additional, Wise, Carol, additional, Sleiman, Patrick M.A., additional, and Hakonarson, Hakon, additional

Published
2020
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11. CLARITY – ChiLdhood Arthritis Risk factor Identification sTudY

Author

Ellis Justine A, Ponsonby Anne-Louise, Pezic Angela, Chavez Raul A, Allen Roger C, Akikusa Jonathan D, and Munro Jane E

Subjects
Juvenile idiopathic arthritis, Epidemiology, Demographics, Early life, Risk factors, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background The aetiology of juvenile idiopathic arthritis (JIA) is largely unknown. We have established a JIA biobank in Melbourne, Australia called CLARITY – ChiLdhood Arthritis Risk factor Identification sTudY, with the broad aim of identifying genomic and environmental disease risk factors. We present here study protocols, and a comparison of socio-demographic, pregnancy, birth and early life characteristics of cases and controls collected over the first 3 years of the study. Methods Cases are children aged ≤18 years with a diagnosis of JIA by 16 years. Controls are healthy children aged ≤18 years, born in the state of Victoria, undergoing a minor elective surgical procedure. Participant families provide clinical, epidemiological and environmental data via questionnaire, and a blood sample is collected. Results Clinical characteristics of cases (n = 262) are similar to those previously reported. Demographically, cases were from families of higher socio-economic status. After taking this into account, the residual pregnancy and perinatal profiles of cases were similar to control children. No case-control differences in breastfeeding commencement or duration were detected, nor was there evidence of increased case exposure to tobacco smoke in utero. At interview, cases were less likely to be exposed to active parental smoking, but disease-related changes to parent behaviour may partly underlie this. Conclusions We show that, after taking into account socio-economic status, CLARITY cases and controls are well matched on basic epidemiological characteristics. CLARITY represents a new study platform with which to generate new knowledge as to the environmental and biological risk factors for JIA.

Published
2012
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12. Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

Author

Ellis Justine A, Munro Jane E, Chavez Raul A, Gordon Lavinia, Joo Jihoon E, Akikusa Jonathan D, Allen Roger C, Ponsonby Anne-Louise, Craig Jeffrey M, and Saffery Richard

Subjects
Epigenetics, Juvenile idiopathic arthritis, DNA methylation, Autoimmunity, Methylome, Methotrexate, Medicine, Genetics, QH426-470
Abstract

Abstract Background Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000 CpGs was compared in a case-control study design. Results Methylation levels were significantly different (FDR adjusted p Conclusions Our data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens.

Published
2012
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13. Establishing an Updated Core Domain Set for Studies in Juvenile Idiopathic Arthritis: A Report from the OMERACT 2018 JIA Workshop

Author

Morgan, Esi M., primary, Munro, Jane E., additional, Horonjeff, Jennifer, additional, Horgan, Ben, additional, Shea, Beverley, additional, Feldman, Brian M., additional, Clairman, Hayyah, additional, Bingham, Clifton O., additional, Thornhill, Susan, additional, Strand, Vibeke, additional, Alongi, Alessandra, additional, Magni-Manzoni, Silvia, additional, van Rossum, Marion A.J., additional, Vesely, Richard, additional, Vojinovic, Jelena, additional, Brunner, Hermine I., additional, Harris, Julia G., additional, Horton, Daniel B., additional, Lovell, Daniel J., additional, Mannion, Melissa, additional, Rahimi, Homaira, additional, Ravelli, Angelo, additional, Ringold, Sarah, additional, Ruperto, Nicolino, additional, Schrandt, M. Suzanne, additional, Shenoi, Susan, additional, Shiff, Natalie J., additional, Toupin-April, Karine, additional, Tzaribachev, Nikolay, additional, Weiss, Pamela, additional, and Consolaro, Alessandro, additional

Published
2019
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14. A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis:challenges and opportunities

Author

Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A., Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E., Niewerth, Martina, Nordal, Ellen Berit, Ruperto, Nicolino, Santos, Maria José, Schanberg, Laura E., Thomson, Wendy, Suijlekom-Smit, Lisette van, Wulffraat, Nico, Hyrich, Kimme, and Pediatrics

Subjects
Medicin och hälsovetenskap, Registry, lcsh:Diseases of the musculoskeletal system, Pharmacosurveillance, Adolescent, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, Medical and Health Sciences, Cohort Studies, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Pediatri: 760, Observational study, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Pediatrics: 760, Journal Article, Humans, Pediatric rheumatology, Registries, Child, lcsh:RJ1-570, Australia, lcsh:Pediatrics, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Rheumatology: 759, Juvenile idiopathic arthritis, Arthritis, Juvenile, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Reumatologi: 759, Europe, Observational Studies as Topic, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, Research Design, Antirheumatic Agents, North America, lcsh:RC925-935, Research Article
Abstract

BackgroundTo characterize the existing national and multinationalregistries and cohortstudies in juvenile idiopathic arthritis (JIA) and identify differences as well asareas of potential future collaboration.MethodsWe surveyed investigators from North America, Europe, and Australia aboutexisting JIA cohort studies and registries. We excluded crosssectionalstudies.We captured information about study design, duration, location, inclusioncriteria, data elements and collection methods.criteria, data elements and collection methods.ResultsWe received survey results from 18 studies, including 11 national and 7 multinationalstudies representing 37 countries in total. Study designs includedinception cohorts, prevalent disease cohorts, and new treatment cohorts (severalof which contribute to pharmacosurveillance activities). Despite numerousdifferences, the data elements collected across the studies was quite similar, withmost studies collecting at least 5 of the 6 American College of Rheumatologycore set variables and the data needed to calculate the 3variableclinical juvenile disease activity score. Most studies were collecting medication initiation anddiscontinuation dates and were attempting to capture serious adverse events.ConclusionThere is a widerange of large, ongoing JIA registries and cohort studies aroundthe world. Our survey results indicate significant potential for futurecollaborative work using data from different studies and both combined andcomparative analyses.

Published
2017
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16. A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis : challenges and opportunities

Author

Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A., Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E., Niewerth, Martina, Nordal, Ellen, Ruperto, Nicolino, Santos, Maria Jose, Schanberg, Laura E., Thomson, Wendy, van Suijlekom-Smit, Lisette, Wulffraat, Nico, Hyrich, Kimme, Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A., Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E., Niewerth, Martina, Nordal, Ellen, Ruperto, Nicolino, Santos, Maria Jose, Schanberg, Laura E., Thomson, Wendy, van Suijlekom-Smit, Lisette, Wulffraat, Nico, and Hyrich, Kimme

Abstract

Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

Published
2017
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17. A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities

Author

Cluster B, Infection & Immunity, Regenerative Medicine and Stem Cells, Child Health, Divisieleiding O&O, BOO, Immunologie/Reumatologie, Infectiezieken, Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A, Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E, Niewerth, Martina, Nordal, Ellen, Ruperto, Nicolino, Santos, Maria Jose, Schanberg, Laura E, Thomson, Wendy, van Suijlekom-Smit, Lisette, Wulffraat, Nico, Hyrich, Kimme, Cluster B, Infection & Immunity, Regenerative Medicine and Stem Cells, Child Health, Divisieleiding O&O, BOO, Immunologie/Reumatologie, Infectiezieken, Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A, Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E, Niewerth, Martina, Nordal, Ellen, Ruperto, Nicolino, Santos, Maria Jose, Schanberg, Laura E, Thomson, Wendy, van Suijlekom-Smit, Lisette, Wulffraat, Nico, and Hyrich, Kimme

Published
2017

18. Evidence for Updating the Core Domain Set of Outcome Measures for Juvenile Idiopathic Arthritis: Report from a Special Interest Group at OMERACT 2016

Author

Morgan, Esi M., primary, Riebschleger, Meredith P., additional, Horonjeff, Jennifer, additional, Consolaro, Alessandro, additional, Munro, Jane E., additional, Thornhill, Susan, additional, Beukelman, Timothy, additional, Brunner, Hermine I., additional, Creek, Emily L., additional, Harris, Julia G., additional, Horton, Daniel B., additional, Lovell, Daniel J., additional, Mannion, Melissa L., additional, Olson, Judyann C., additional, Rahimi, Homaira, additional, Gallo, Maria Chiara, additional, Calandra, Serena, additional, Ravelli, Angelo, additional, Ringold, Sarah, additional, Shenoi, Susan, additional, Stinson, Jennifer, additional, Toupin-April, Karine, additional, Strand, Vibeke, additional, and Bingham, Clifton O., additional

Published
2017
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19. A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities

Author

Beukelman, Timothy, primary, Anink, Janneke, additional, Berntson, Lillemor, additional, Duffy, Ciaran, additional, Ellis, Justine A., additional, Glerup, Mia, additional, Guzman, Jaime, additional, Horneff, Gerd, additional, Kearsley-Fleet, Lianne, additional, Klein, Ariane, additional, Klotsche, Jens, additional, Magnusson, Bo, additional, Minden, Kirsten, additional, Munro, Jane E., additional, Niewerth, Martina, additional, Nordal, Ellen, additional, Ruperto, Nicolino, additional, Santos, Maria Jose, additional, Schanberg, Laura E., additional, Thomson, Wendy, additional, van Suijlekom-Smit, Lisette, additional, Wulffraat, Nico, additional, and Hyrich, Kimme, additional

Published
2017
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20. Association of Increased Sun Exposure Over the Life‐course with a Reduced Risk of Juvenile Idiopathic Arthritis.

Author

Chiaroni‐Clarke, Rachel C., Munro, Jane E., Pezic, Angela, Cobb, Joanna E., Akikusa, Jonathan D., Allen, Roger C., Dwyer, Terence, Ponsonby, Anne‐Louise, and Ellis, Justine A.

Subjects
*JUVENILE idiopathic arthritis, *BEHAVIOR, *SUN, *DOSE-response relationship in biochemistry, *BEHAVIORAL assessment, *VITAMINS
Abstract

Cutaneous sun exposure is an important determinant of circulating vitamin D. Both sun exposure and vitamin D have been inversely associated with risk of autoimmune disease. In juvenile idiopathic arthritis (JIA), low circulating vitamin D appears common, but disease‐related behavioral changes may have influenced sun exposure. We therefore aimed to determine whether predisease sun exposure is associated with JIA. Using validated questionnaires, we retrospectively measured sun exposure for 202 Caucasian JIA case–control pairs born in Victoria Australia, matched for birth year and time of recruitment. Measures included maternal sun exposure at 12 weeks of pregnancy and child sun exposure across the life‐course prediagnosis. We converted exposure to UVR dose and looked for case–control differences using logistic regression, adjusting for potential confounders. Higher cumulative prediagnosis UVR exposure was associated with reduced risk of JIA, with a clear dose–response relationship (trend P = 0.04). UVR exposure at 12 weeks of pregnancy was similarly inversely associated with JIA (trend P = 0.011). Associations were robust to sensitivity analyses for prediagnosis behavioral changes, disease duration and knowledge of the hypothesis. Our data indicate that lower UVR exposure may increase JIA risk. This may be through decreased circulating vitamin D, but prospective studies are required to confirm this. [ABSTRACT FROM AUTHOR]

Published
2019
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21. Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility

Author

Finkel, Terri H., primary, Li, Jin, additional, Wei, Zhi, additional, Wang, Wei, additional, Zhang, Haitao, additional, Behrens, Edward M., additional, Reuschel, Emma L., additional, Limou, Sophie, additional, Wise, Carol, additional, Punaro, Marilynn, additional, Becker, Mara L., additional, Munro, Jane E., additional, Flatø, Berit, additional, Førre, Øystein, additional, Thompson, Susan D., additional, Langefeld, Carl D., additional, Glass, David N., additional, Glessner, Joseph T., additional, Kim, Cecilia E., additional, Frackelton, Edward, additional, Shivers, Debra K., additional, Thomas, Kelly A., additional, Chiavacci, Rosetta M., additional, Hou, Cuiping, additional, Xu, Kexiang, additional, Snyder, James, additional, Qiu, Haijun, additional, Mentch, Frank, additional, Wang, Kai, additional, Winkler, Cheryl A., additional, Lie, Benedicte A., additional, Ellis, Justine A., additional, and Hakonarson, Hakon, additional

Published
2016
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22. DNA methylation at IL32 in juvenile idiopathic arthritis

Author

Meyer, Braydon, Chavez, Raul A., Munro, Jane E., Chiaroni-Clarke, Rachel C., Akikusa, Jonathan D., Allen, Roger C., Craig, Jeffrey M., Ponsonby, Anne-Louise, Saffery, Richard, Ellis, Justine A., Meyer, Braydon, Chavez, Raul A., Munro, Jane E., Chiaroni-Clarke, Rachel C., Akikusa, Jonathan D., Allen, Roger C., Craig, Jeffrey M., Ponsonby, Anne-Louise, Saffery, Richard, and Ellis, Justine A.

Published
2015

23. Genetic sharing and heritability of paediatric age of onset autoimmune diseases.

Author

Li, Yun R, Zhao, Sihai D, Li, Jin, Bradfield, Jonathan P, Mohebnasab, Maede, Steel, Laura, Kobie, Julie, Abrams, Debra J, Mentch, Frank D, Glessner, Joseph T, Guo, Yiran, Wei, Zhi, Connolly, John J, Cardinale, Christopher J, Bakay, Marina, Li, Dong, Maggadottir, S Melkorka, Thomas, Kelly A, Qui, Haijun, Chiavacci, Rosetta M, Kim, Cecilia E, Wang, Fengxiang, Snyder, James, Flatø, Berit, Førre, Øystein, Denson, Lee A, Thompson, Susan D, Becker, Mara L, Guthery, Stephen L, Latiano, Anna, Perez, Elena, Resnick, Elena, Strisciuglio, Caterina, Staiano, Annamaria, Miele, Erasmo, Silverberg, Mark S, Lie, Benedicte A, Punaro, Marilynn, Russell, Richard K, Wilson, David C, Dubinsky, Marla C, Monos, Dimitri S, Annese, Vito, Munro, Jane E, Wise, Carol, Chapel, Helen, Cunningham-Rundles, Charlotte, Orange, Jordan S, Behrens, Edward M, Sullivan, Kathleen E, Kugathasan, Subra, Griffiths, Anne M, Satsangi, Jack, Grant, Struan FA, Sleiman, Patrick MA, Finkel, Terri H, Polychronakos, Constantin, Baldassano, Robert N, Luning Prak, Eline T, Ellis, Justine A, Li, Hongzhe, Keating, Brendan J, Hakonarson, Hakon, Li, Yun R, Zhao, Sihai D, Li, Jin, Bradfield, Jonathan P, Mohebnasab, Maede, Steel, Laura, Kobie, Julie, Abrams, Debra J, Mentch, Frank D, Glessner, Joseph T, Guo, Yiran, Wei, Zhi, Connolly, John J, Cardinale, Christopher J, Bakay, Marina, Li, Dong, Maggadottir, S Melkorka, Thomas, Kelly A, Qui, Haijun, Chiavacci, Rosetta M, Kim, Cecilia E, Wang, Fengxiang, Snyder, James, Flatø, Berit, Førre, Øystein, Denson, Lee A, Thompson, Susan D, Becker, Mara L, Guthery, Stephen L, Latiano, Anna, Perez, Elena, Resnick, Elena, Strisciuglio, Caterina, Staiano, Annamaria, Miele, Erasmo, Silverberg, Mark S, Lie, Benedicte A, Punaro, Marilynn, Russell, Richard K, Wilson, David C, Dubinsky, Marla C, Monos, Dimitri S, Annese, Vito, Munro, Jane E, Wise, Carol, Chapel, Helen, Cunningham-Rundles, Charlotte, Orange, Jordan S, Behrens, Edward M, Sullivan, Kathleen E, Kugathasan, Subra, Griffiths, Anne M, Satsangi, Jack, Grant, Struan FA, Sleiman, Patrick MA, Finkel, Terri H, Polychronakos, Constantin, Baldassano, Robert N, Luning Prak, Eline T, Ellis, Justine A, Li, Hongzhe, Keating, Brendan J, and Hakonarson, Hakon

Abstract

Autoimmune diseases (AIDs) are polygenic diseases affecting 7-10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h(2)). SNP-h(2) estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h(2) in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

Published
2015

24. Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Author

Li, Yun R., primary, Zhao, Sihai D., additional, Li, Jin, additional, Bradfield, Jonathan P., additional, Mohebnasab, Maede, additional, Steel, Laura, additional, Kobie, Julie, additional, Abrams, Debra J., additional, Mentch, Frank D., additional, Glessner, Joseph T., additional, Guo, Yiran, additional, Wei, Zhi, additional, Connolly, John J., additional, Cardinale, Christopher J., additional, Bakay, Marina, additional, Li, Dong, additional, Maggadottir, S. Melkorka, additional, Thomas, Kelly A., additional, Qui, Haijun, additional, Chiavacci, Rosetta M., additional, Kim, Cecilia E., additional, Wang, Fengxiang, additional, Snyder, James, additional, Flatø, Berit, additional, Førre, Øystein, additional, Denson, Lee A., additional, Thompson, Susan D., additional, Becker, Mara L., additional, Guthery, Stephen L., additional, Latiano, Anna, additional, Perez, Elena, additional, Resnick, Elena, additional, Strisciuglio, Caterina, additional, Staiano, Annamaria, additional, Miele, Erasmo, additional, Silverberg, Mark S., additional, Lie, Benedicte A., additional, Punaro, Marilynn, additional, Russell, Richard K., additional, Wilson, David C., additional, Dubinsky, Marla C., additional, Monos, Dimitri S., additional, Annese, Vito, additional, Munro, Jane E., additional, Wise, Carol, additional, Chapel, Helen, additional, Cunningham-Rundles, Charlotte, additional, Orange, Jordan S., additional, Behrens, Edward M., additional, Sullivan, Kathleen E., additional, Kugathasan, Subra, additional, Griffiths, Anne M., additional, Satsangi, Jack, additional, Grant, Struan F. A., additional, Sleiman, Patrick M. A., additional, Finkel, Terri H., additional, Polychronakos, Constantin, additional, Baldassano, Robert N., additional, Luning Prak, Eline T., additional, Ellis, Justine A., additional, Li, Hongzhe, additional, Keating, Brendan J., additional, and Hakonarson, Hakon, additional

Published
2015
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25. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Author

Li, Yun R, primary, Li, Jin, additional, Zhao, Sihai D, additional, Bradfield, Jonathan P, additional, Mentch, Frank D, additional, Maggadottir, S Melkorka, additional, Hou, Cuiping, additional, Abrams, Debra J, additional, Chang, Diana, additional, Gao, Feng, additional, Guo, Yiran, additional, Wei, Zhi, additional, Connolly, John J, additional, Cardinale, Christopher J, additional, Bakay, Marina, additional, Glessner, Joseph T, additional, Li, Dong, additional, Kao, Charlly, additional, Thomas, Kelly A, additional, Qiu, Haijun, additional, Chiavacci, Rosetta M, additional, Kim, Cecilia E, additional, Wang, Fengxiang, additional, Snyder, James, additional, Richie, Marylyn D, additional, Flatø, Berit, additional, Førre, Øystein, additional, Denson, Lee A, additional, Thompson, Susan D, additional, Becker, Mara L, additional, Guthery, Stephen L, additional, Latiano, Anna, additional, Perez, Elena, additional, Resnick, Elena, additional, Russell, Richard K, additional, Wilson, David C, additional, Silverberg, Mark S, additional, Annese, Vito, additional, Lie, Benedicte A, additional, Punaro, Marilynn, additional, Dubinsky, Marla C, additional, Monos, Dimitri S, additional, Strisciuglio, Caterina, additional, Staiano, Annamaria, additional, Miele, Erasmo, additional, Kugathasan, Subra, additional, Ellis, Justine A, additional, Munro, Jane E, additional, Sullivan, Kathleen E, additional, Wise, Carol A, additional, Chapel, Helen, additional, Cunningham-Rundles, Charlotte, additional, Grant, Struan F A, additional, Orange, Jordan S, additional, Sleiman, Patrick M A, additional, Behrens, Edward M, additional, Griffiths, Anne M, additional, Satsangi, Jack, additional, Finkel, Terri H, additional, Keinan, Alon, additional, Prak, Eline T Luning, additional, Polychronakos, Constantin, additional, Baldassano, Robert N, additional, Li, Hongzhe, additional, Keating, Brendan J, additional, and Hakonarson, Hakon, additional

Published
2015
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26. DNA methylation at IL32 in juvenile idiopathic arthritis

Author

Meyer, Braydon, primary, Chavez, Raul A., additional, Munro, Jane E., additional, Chiaroni-Clarke, Rachel C., additional, Akikusa, Jonathan D., additional, Allen, Roger C., additional, Craig, Jeffrey M., additional, Ponsonby, Anne-Louise, additional, Saffery, Richard, additional, and Ellis, Justine A., additional

Published
2015
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28. Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

Author

Ellis, Justine A, Munro, Jane E, Chavez, Raul A, Gordon, Lavinia, Joo, Jihoon E, Akikusa, Jonathan D, Allen, Roger C, Ponsonby, Anee-Louise, Craig, Jeffrey M, Saffery, Richard, Ellis, Justine A, Munro, Jane E, Chavez, Raul A, Gordon, Lavinia, Joo, Jihoon E, Akikusa, Jonathan D, Allen, Roger C, Ponsonby, Anee-Louise, Craig, Jeffrey M, and Saffery, Richard

Abstract

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000 CpGs was compared in a case-control study design. RESULTS: Methylation levels were significantly different (FDR adjusted p<0.1) at 145 loci. Removal of four samples exposed to methotrexate had a striking impact on the outcome of the analysis, reducing the number of differentially methylated loci to 11. The methotrexate-naive analysis identified reduced methylation at the gene encoding the pro-inflammatory cytokine IL32, which was subsequently replicated using a second analysis platform and a second set of case-control pairs. CONCLUSIONS: Our data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens.

Published
2012

32. Genomic risk scores for juvenile idiopathic arthritis and its subtypes

Author

Cánovas, Rodrigo, Cobb, Joanna, Brozynska, Marta, Bowes, John, Li, Yun R, Smith, Samantha Louise, Hakonarson, Hakon, Thomson, Wendy, Ellis, Justine A, Abraham, Gad, Munro, Jane E, and Inouye, Michael

Subjects
musculoskeletal diseases, Male, genetic structures, rheumatoid, Adolescent, Polymorphism, Single Nucleotide, Arthritis, Juvenile, 3. Good health, polymorphism, Cohort Studies, Machine Learning, juvenile, arthritis, immune system diseases, Risk Factors, Humans, Female, Genetic Predisposition to Disease, genetic, skin and connective tissue diseases, Child
Abstract

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance. METHODS: We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts. RESULTS: The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively. CONCLUSIONS: A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.

33. A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities

Author

Beukelman, Timothy, Anink, Janneke, Berntson, Lillemor, Duffy, Ciaran, Ellis, Justine A, Glerup, Mia, Guzman, Jaime, Horneff, Gerd, Kearsley-Fleet, Lianne, Klein, Ariane, Klotsche, Jens, Magnusson, Bo, Minden, Kirsten, Munro, Jane E, Niewerth, Martina, Nordal, Ellen, Ruperto, Nicolino, Santos, Maria J, Schanberg, Laura E, Thomson, Wendy, Van Suijlekom-Smit, Lisette, Wulffraat, Nico, and Hyrich, Kimme

Subjects
10. No inequality, 3. Good health
Abstract

Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

34. Genomic risk scores for juvenile idiopathic arthritis and its subtypes

Author

Cánovas, Rodrigo, Cobb, Joanna, Brozynska, Marta, Bowes, John, Li, Yun R, Smith, Samantha Louise, Hakonarson, Hakon, Thomson, Wendy, Ellis, Justine A, Abraham, Gad, Munro, Jane E, and Inouye, Michael

Subjects
musculoskeletal diseases, genetic structures, rheumatoid, 3. Good health, polymorphism, juvenile, arthritis, immune system diseases, Rheumatoid arthritis, genetic, skin and connective tissue diseases
Abstract

Objectives: Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance. Methods: We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts. Results: The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively. Conclusions: A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.

35. Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Author

Jin Li, Patrick M. A. Sleiman, Rosetta M. Chiavacci, Dimitri S. Monos, Fengxiang Wang, Zhi Wei, Jane E Munro, Edward M. Behrens, Carol Wise, Kathleen E. Sullivan, Jack Satsangi, Jordan S. Orange, Sihai Dave Zhao, Subramaniam Kugathasan, Maede Mohebnasab, Vito Annese, Elena S. Resnick, Charlotte Cunningham-Rundles, Eline T. Luning Prak, Constantin Polychronakos, Christopher J. Cardinale, Haijun Qui, Kelly A. Thomas, David C. Wilson, Cecilia E. Kim, Yiran Guo, Marina Bakay, Julie Kobie, Brendan J. Keating, Elena E. Perez, Frank D. Mentch, Marla Dubinsky, Richard K Russell, Hakon Hakonarson, Stephen L. Guthery, Berit Flatø, Justine A. Ellis, Susan D. Thompson, Struan F.A. Grant, Øystein Førre, James Snyder, Benedicte A. Lie, Marilynn Punaro, Erasmo Miele, Yun Li, Mara L. Becker, Debra J. Abrams, S. Melkorka Maggadottir, Annamaria Staiano, Caterina Strisciuglio, Lee A. Denson, Terri H. Finkel, John Connolly, Dong Li, Hongzhe Li, Helen Chapel, Robert N. Baldassano, Anne M. Griffiths, Anna Latiano, Mark S. Silverberg, Jonathan P. Bradfield, Laura Steel, Joseph T. Glessner, Li, Yun R., Zhao, Sihai D., Li, Jin, Bradfield, Jonathan P., Mohebnasab, Maede, Steel, Laura, Kobie, Julie, Abrams, Debra J., Mentch, Frank D., Glessner, Joseph T., Guo, Yiran, Wei, Zhi, Connolly, John J., Cardinale, Christopher J., Bakay, Marina, Li, Dong, Maggadottir, S. Melkorka, Thomas, Kelly A., Qui, Haijun, Chiavacci, Rosetta M., Kim, Cecilia E., Wang, Fengxiang, Snyder, Jame, Flatø, Berit, Førre, Oystein, Denson, Lee A., Thompson, Susan D., Becker, Mara L., Guthery, Stephen L., Latiano, Anna, Perez, Elena, Resnick, Elena, Strisciuglio, Caterina, Staiano, Annamaria, Miele, Erasmo, Silverberg, Mark S., Lie, Benedicte A., Punaro, Marilynn, Russell, Richard K., Wilson, David C., Dubinsky, Marla C., Monos, Dimitri S., Annese, Vito, Munro, Jane E., Wise, Carol, Chapel, Helen, Cunningham Rundles, Charlotte, Orange, Jordan S., Behrens, Edward M., Sullivan, Kathleen E., Kugathasan, Subra, Griffiths, Anne M., Satsangi, Jack, Grant, Struan F. A., Sleiman, Patrick M. A., Finkel, Terri H., Polychronakos, Constantin, Baldassano, Robert N., Luning Prak, Eline T., Ellis, Justine A., Li, Hongzhe, Keating, Brendan J., and Hakonarson, Hakon

Subjects
Male, Adolescent, Population, European Continental Ancestry Group, General Physics and Astronomy, Genome-wide association study, Biology, Major histocompatibility complex, Inflammatory bowel disease, Autoimmune Disease, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, Article, Autoimmune Diseases, 03 medical and health sciences, Physics and Astronomy (all), 0302 clinical medicine, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, education, Child, 030304 developmental biology, 030203 arthritis & rheumatology, Genetics, 0303 health sciences, education.field_of_study, Multidisciplinary, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Case-control study, General Chemistry, Heritability, medicine.disease, 3. Good health, Rheumatoid arthritis, Case-Control Studies, Child, Preschool, biology.protein, Female, Age of onset, Case-Control Studie, Genome-Wide Association Study, Human
Abstract

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts., Autoimmune diseases are genetically complex disorders that affect up to 10% of the Western population. Here Li et al. quantify the heritability of a range of autoimmune diseases in the largest paediatric cohort examined to date, illustrating that genetic and non-genetic components variably contribute to the susceptibility of each disease.

Published
2015
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36. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Author

Marina Bakay, Diana Chang, Kelly A. Thomas, Jack Satsangi, Sihai Dave Zhao, Cuiping Hou, Carol Wise, Dong Li, Feng Gao, Anne M. Griffiths, Brendan J. Keating, Jane E Munro, Jin Li, Berit Flatø, Øystein Førre, Marla Dubinsky, Benedicte A. Lie, Charlotte Cunningham-Rundles, Erasmo Miele, Debra J. Abrams, Elena S. Resnick, Edward M. Behrens, Haijun Qiu, Marilynn Punaro, Anna Latiano, Alon Keinan, David C. Wilson, Christopher J. Cardinale, John Connolly, Lee A. Denson, Mark S. Silverberg, Subra Kugathasan, Jonathan P. Bradfield, Dimitri S. Monos, Fengxiang Wang, Richard K Russell, Annamaria Staiano, Hakon Hakonarson, Caterina Strisciuglio, Justine A. Ellis, Stephen L. Guthery, Hongzhe Li, Terri H. Finkel, Helen Chapel, Marylyn D Richie, James Snyder, S. Melkorka Maggadottir, Elena E. Perez, Rosetta M. Chiavacci, Kathleen E. Sullivan, Struan F.A. Grant, Robert N. Baldassano, Jordan S. Orange, Eline T. Luning Prak, Vito Annese, Constantin Polychronakos, Cecilia E. Kim, Yiran Guo, Frank D. Mentch, Susan D. Thompson, Charlly Kao, Yun Li, Mara L. Becker, Zhi Wei, Joseph T. Glessner, Patrick M. A. Sleiman, Li, Yun R., Li, Jin, Zhao, Sihai D., Bradfield, Jonathan P., Mentch, Frank D., Maggadottir, S. Melkorka, Hou, Cuiping, Abrams, Debra J., Chang, Diana, Gao, Feng, Guo, Yiran, Wei, Zhi, Connolly, John J., Cardinale, Christopher J., Bakay, Marina, Glessner, Joseph T., Li, Dong, Kao, Charlly, Thomas, Kelly A., Qiu, Haijun, Chiavacci, Rosetta M., Kim, Cecilia E., Wang, Fengxiang, Snyder, Jame, Richie, Marylyn D., Flatø, Berit, Førre, Øystein, Denson, Lee A., Thompson, Susan D., Becker, Mara L., Guthery, Stephen L., Latiano, Anna, Perez, Elena, Resnick, Elena, Russell, Richard K., Wilson, David C., Silverberg, Mark S., Annese, Vito, Lie, Benedicte A., Punaro, Marilynn, Dubinsky, Marla C., Monos, Dimitri S., Strisciuglio, Caterina, Staiano, Annamaria, Miele, Erasmo, Kugathasan, Subra, Ellis, Justine A., Munro, Jane E., Sullivan, Kathleen E., Wise, Carol A., Chapel, Helen, Cunningham Rundles, Charlotte, Grant, Struan F. A., Orange, Jordan S., Sleiman, Patrick M. A., Behrens, Edward M., Griffiths, Anne M., Satsangi, Jack, Finkel, Terri H., Keinan, Alon, Prak, Eline T. Luning, Polychronakos, Constantin, Baldassano, Robert N., Li, Hongzhe, Keating, Brendan J., and Hakonarson, Hakon

Subjects
Candidate gene, Population, Quantitative Trait Loci, Single-nucleotide polymorphism, Genome-wide association study, Quantitative trait locus, Autoimmune Disease, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Risk Factors, Humans, Medicine, education, Child, Genetic association, Genetics, education.field_of_study, Biochemistry, Genetics and Molecular Biology (all), business.industry, Risk Factor, Medicine (all), General Medicine, Genetic architecture, Expression quantitative trait loci, Immunology, business, Genome-Wide Association Study, Human
Abstract

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases.

Published
2015
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